Biophysical Society Thematic Meeting | Bucharest 2026

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Biophysical Society Thematic Meetings

PROGRAM AND ABSTRACTS

Biophysics of Membrane Reactions in the Brain

Bucharest, Romania | May 11–14, 2026

Organizing Committee

Ana-Nicoleta Bondar, University of Bucharest, Romania Kumiko Hayashi, The University of Tokyo, Japan Kalina Hristova, Johns Hopkins University, USA

Thank You to Our Sponsors

Thank you to all sponsors for their support.

Biophysics of Membrane Reactions in Brian

Welcome Letter

April 2026

Dear Colleagues,

We would like to welcome you to the Biophysical Society Thematic Meeting entitled, Biophysics of Membrane Reactions in the Brain . This highly interdisciplinary Thematic Meeting will bring together basic science with cutting edge applications to study neurological disorders, brain disease, and cellular signalling pathways of fundamental importance to physiology and disease. The central theme of the meeting is the study of membrane reactions which are part of cellular signalling pathways implicated in brain function. Overall, this conference will feature 15 posters, 49 invited and contributed talks, and bring together over 65 scientists from a wide range of backgrounds and expertise. We hope that this meeting will not only provide a place to share your recent findings, but also to help promote new collaborations, helpful discussions, and future connections. We invite you all to actively take part in the discussions following each talk, the poster sessions, and the informal exchanges that will be possible during the coffee breaks and meals. We also hope that you will also enjoy the beautiful city of Bucharest!

We would like to thank the University of Bucharest for their support of this meeting.

The Organizing Committee Ana-Nicoleta Bondar

Kalina Hristova Kumiko Hayashi

Biophysics of Membrane Reactions in Brian

Code of Conduct

Biophysical Society Code of Conduct, Anti-Harassment Policy The Biophysical Society (BPS) is committed to providing an environment that encourages the free expression and exchange of scientific ideas. As a global, professional Society, the BPS is committed to the philosophy of equal opportunity and respectful treatment for all, regardless of national or ethnic origin, religion or religious belief, gender, gender identity or expression, race, color, age, marital status, sexual orientation, disabilities, veteran status, or any other reason not related to scientific merit. All BPS meetings and BPS-sponsored activities promote an environment that is free of inappropriate behavior and harassment by or toward all attendees and participants of Society events, including speakers, organizers, students, guests, media, exhibitors, staff, vendors, and other suppliers. BPS expects anyone associated with an official BPS-sponsored event to respect the rules and policies of the Society, the venue, the hotels, and the city. Definition of Harassment The term “harassment” includes but is not limited to epithets, unwelcome slurs, jokes, or verbal, graphic or physical conduct relating to an individual’s race, color, religious creed, sex, national origin, ancestry, citizenship status, age, gender or sexual orientation that denigrate or show hostility or aversion toward an individual or group. Sexual harassment refers to unwelcome sexual advances, requests for sexual favors, and other verbal or physical conduct of a sexual nature. Behavior and language that are welcome/acceptable to one person may be unwelcome/offensive to another. Consequently, individuals must use discretion to ensure that their words and actions communicate respect for others. This is especially important for those in positions of authority since individuals with lower rank or status may be reluctant to express their objections or discomfort regarding unwelcome behavior. It does not refer to occasional compliments of a socially acceptable nature. It refers to behavior that is not welcome, is personally offensive, debilitates morale, and therefore, interferes with work effectiveness. The following are examples of behavior that, when unwelcome, may constitute sexual harassment: sexual flirtations, advances, or propositions; verbal comments or physical actions of a sexual nature; sexually degrading words used to describe an individual; a display of sexually suggestive objects or pictures; sexually explicit jokes; unnecessary touching. Attendees or participants who are asked to stop engaging in harassing behavior are expected to comply immediately. Anyone who feels harassed is encouraged to immediately inform the alleged harasser that the behavior is unwelcome. In many instances, the person is unaware that their conduct is offensive and when so advised can easily and willingly correct the conduct so that it does not reoccur. Anyone who feels harassed is NOT REQUIRED to address the person believed guilty of inappropriate treatment. If the informal discussion with the alleged harasser is unsuccessful in remedying the problem or if the complainant does not feel comfortable with such an approach, they can report the behavior as detailed below. Reported or suspected occurrences of harassment will be promptly and thoroughly investigated. Following an investigation, BPS will immediately take any necessary and appropriate action. BPS will not permit or condone any acts of retaliation against anyone who files harassment complaints or cooperates in the investigation of same. Reporting a Violation Violations of this Conduct Policy should be reported immediately. If you feel physically unsafe or believe a crime has been committed, you should report it to the police immediately. To report a violation to BPS:

• You may do so in person at the Annual Meeting at the BPS Business Office in the convention center.

Biophysics of Membrane Reactions in Brian

Code of Conduct

• You may do so in person to BPS senior staff at Thematic Meetings, BPS Conferences, or other BPS events.

• At any time (during or after an event), you can make a report through

http://biophysics.ethicspoint.com or via a dedicated hotline (phone numbers listed on the website) which will collect and relay information in a secure and sensitive manner.

Reported or suspected occurrences of harassment will be promptly and thoroughly investigated per the procedure detailed below. Following an investigation, BPS will immediately take any necessary and appropriate action. BPS will not permit or condone any acts of retaliation against anyone who files harassment complaints or cooperates in the investigation of same. Investigative Procedure All reports of harassment or sexual harassment will be treated seriously. However, absolute confidentiality cannot be promised nor can it be assured. BPS will conduct an investigation of any complaint of harassment or sexual harassment, which may require limited disclosure of pertinent information to certain parties, including the alleged harasser. Once a complaint of harassment or sexual harassment is received, BPS will begin a prompt and thorough investigation. Please note, if a complaint is filed anonymously, BPS may be severely limited in our ability to follow-up on the allegation. • An impartial investigative committee, consisting of the current President, President-Elect, and Executive Officer will be established. If any of these individuals were to be named in an allegation, they would be excluded from the committee. • The committee will interview the complainant and review the written complaint. If no written complaint exists, one will be requested. • The committee will speak to the alleged offender and present the complaint. • The alleged offender will be given the opportunity to address the complaint, with sufficient time to respond to the evidence and bring his/her own evidence. • If the facts are in dispute, the investigative team may need to interview anyone named as witnesses. • The investigative committee may seek BPS Counsel’s advice. • Once the investigation is complete, the committee will report their findings and make recommendations to the Society Officers. • If the severity of the allegation is high, is a possible repeat offense, or is determined to be beyond BPS’s capacity to assess claims and views on either side, BPS may refer the case to the alleged offender’s home institution (Office of Research Integrity of similar), employer, licensing board, or law enforcement for their investigation and decision. Disciplinary Actions Individuals engaging in behavior prohibited by this policy as well as those making allegations of harassment in bad faith will be subject to disciplinary action. Such actions range from a written warning to ejection from the meeting or activity in question without refund of registration fees, being banned from participating in future Society meetings or Society-sponsored activities, being expelled from membership in the Society, and reporting the behavior to their employer or calling the authorities. In the event that the individual is dissatisfied with the results of the investigation, they may appeal to the President of the Society. Any questions regarding this policy should be directed to the BPS Executive Officer or other Society Officer.

Biophysics of Membrane Reactions in Brian

Table of Contents

Table of Contents

General Information……………………………………………………………………………....1 Program Schedule..……………………………………………………………………………….3 Speaker Abstracts………………………………………………………………………………...8 Poster Sessions…………………………………………………………………………………...55

Biophysics of Membrane Reactions in Brian

General Information

GENERAL INFORMATION

Registration/Information Location and Hours The meeting will take place at the Casa Universitarilor a Universit ăţ ii din Bucure ṣ ti (The University House of the University of Bucharest), located at Str. Dionisie Lupu, nr. 46, Sector 1 Bucharest 010455, Romania. The BPS Registration Desk, to pick up your badge and meeting materials, will be located in building during the following times: Monday, May 11 14:00 – 16:00 Tuesday, May 12 8:30 – 18:30 Wednesday, May 13 8:30 – 15:00 Thursday, May 14 8:30 – 17:00 Instructions for Presentations (1) Presentation Facilities: A data projector will be available in the Auditorium. Speakers are required to bring their own laptops and adaptors. It is recommended to have a backup of the presentation on a USB drive in case of any unforeseen circumstances. Speakers are advised to preview their final presentations before the start of each session. (2) Poster Session: 1) All poster sessions will be held in the University House Building. 2) A display board measuring 85 cm wide x 200 cm high (portrait style) will be provided for each poster. Poster should be printed in A0 format 84.1 cm wide x 118.9 cm high (portrait orientation). Poster boards are numbered according to the same numbering scheme as listed in the E-book. 3) Please note that there is no designated time for poster presentations. Posters will be available for viewing throughout the meeting during coffee breaks and lunch periods.

4) All posters left uncollected at the end of the meeting will be discarded.

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General Information

Note Pads/Pens Society pens will be provided, however please bring your own note pad. Meals, Coffee Breaks, and Socials

All food functions will be served in the dining area. Registration includes a Welcome Buffet & Networking on Monday evening from 18:00 – 20:00, Coffee Breaks (Tuesday, Wednesday, and Thursday), Lunches (Tuesday, Wednesday, and Thursday), and Dinner Buffet and Networking on Thursday Evening from 17:05 – 18:15. Smoking Please be advised that the Casa Universitarilor a Universit ăţ ii din Bucure ṣ ti (The University House of the University of Bucharest) is a non-smoking facility. Name Badges Name badges will be given to you when you check-in at the Registration Desk. Please wear your badge throughout the conference. Internet Wi-Fi will be provided at the venue. Information will be available at the registration desk. On-Site Contact Information If you have any further requirements during the meeting, please contact the meeting staff at the registration desk from May 11-14 during registration hours. In case of emergency, you may contact the following: Dorothy Chaconas Phone: 301-785-0802 Email: dchaconas@biophysics.org

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Speaker Abstracts

Monday, May 11, 2026

14:00 – 16:00

Registration and Get-Together

16:00 – 16:30

Welcome and Opening Remarks Welcome from the Chairs

Welcome from Carmen Chifiriuc, Vice-Rector of Research Welcome from Marian Preda, University of Bucharest Rector Welcome from Andrei Luca, Diplomacy of the Ministry of Foreign Affairs Membrane Reactions in the Brain Chair: Ana-Nicoleta Bondar, University of Bucharest, Romania Keynote Lecture: Gabriela Popescu, University of Buffalo, USA NMDA Receptor: Operation and Modulatory Mechanisms Future of Biophysics: Kota Katayama, Nagoya Institute of Technology, Japan Spectroscopic Insights into the Molecular Mechanisms Underlying Biased GPCR Signaling Biophysics Meets Philosophy: Andrei Ionu ţ M ă r ăş oiu, University of Bucharest, Romania Representation and Design in Network Models of Category Deficits Vasanthi Jayaraman, University of Texas Health Science Center at Houston, USA Subtype-Specific Conformational Landscapes Govern NMDA Receptor Gating

Session I

16:30 – 17:10

17:10 – 17:35

17:35 – 18:00

18:00 – 18:25

18:25 – 20:00

Welcome Buffet & Networking

Tuesday, May 12, 2026 8:30 – 18:30

Registration/Information

Session II

Neurological Disorders Chair: David Minh, Illinois Institute of Technology, USA

9:00 – 9:25

David Minh, Illinois Institute of Technology, USA ML Mapping of GPCR Intracellular Pocket Conformations to Multidimensional Pharmacological Efficacy Marçal Vilar, Instituto de Biomedicina de Valencia, Spain Cleavage at the Membrane: How Gamma-Secretase Complex Modulates Neuronal Complexity . Liviu Movileanu, Syracuse University, USA Membrane Protein Engineering for Sensing Transient Molecular Hallmarks in Neurodegeneration Lila Gordon, NIH, USA * Correlating Clathrin Structures with Endocytic Defects in Alzheimer’s Disease

9:25 – 9:50

9:50 – 10:15

10:15 – 10:30

10:30 – 11:00

Coffee Break & Posters

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Speaker Abstracts

Session III

Understanding the Aqueous and the Membrane Environments Chair: Mariana Pinteala, Institute for Macromolecular Chemistry, RAS, Romania William Wimley, Tulane University, USA PH-Responsive Peptide Nanoparticles Deliver Macromolecules to Cells via Endosomal Membrane Nanoporation Ingela Parmryd, University of Gothenburg, Sweden Membrane Topography Variations and Quantitative Biology - Pitfalls and Solutions Elena Pohl, University of Veterinary Medicine Vienna, Austria Mitochondrial Uncoupling Protein 4 in Brain: Putative Functions and Molecular Mechanisms Nicolas Vitale, Institute of Cellular and Integrative Neurosciences, CNRS, France * Illuminating Neurosecretion: Optogenetic and Click Chemistry Novel Tools to Highlight the Multiple Roles of Phosphatidic Acid in Neurotransmitter Release

11:00 – 11:25

11:25 – 11:50

11:50 – 12:15

12:15 – 12:30

12:30 – 14:00

Lunch & Posters

Session IV

Signaling in the Brain Chair: Kumiko Hayashi, The University of Tokyo, Japan

14:00 – 14:25

Rohit Menon, University of Regensburg, Germany Differential Oxytocin Receptor Signaling Drives the Reversal of Social Trauma Induced Avoidance in Mice

14:25 – 14:50

Christoph Fahlke, Forschungszentrum Jülich GmbH, Germany Molecular Physiology of Vesicular Glutamate Transporters

14:50 – 15:05

Jan Steinkühler, Kiel University, Germany * Lipid Nanotubes A Model System for Neuron Signaling and Morphological Plasticity Katharina Duerr, University of Oxford, United Kingdom * Structural Mechanism of Membrane Transport and Allosteric Regulation in KCC2, A Key Regulator of Neuronal Inhibition

15:05 – 15:20

15:20 – 15:40

Coffee Break & Posters

Session V

Signaling Across the Membrane Part I Chair: Ching-Ju Tsai, Paul Scherrer Institute, Switzerland

15:40 – 16:05

Leonid Sazanov, Institute of Science and Technology Austria (ISTA), Austria How the Twin-Arginine Translocase (Tat) System Transports Folded Proteins Across Membranes Without Leaking Protons? Matthias Buck, Case Western Reserve University, USA Understanding Protein-Protein and Protein-Membrane Interactions in the Plexin Transmembrane Receptor for Axon Guidance: A Perspective from Structural Biology, Binding Biophysics and Molecular Dynamics Simulations as Well as AI Based Modeling

16:05 – 16:30

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Speaker Abstracts

16:30 – 16:55

Durba Sengupta, CSIR-National Chemical Laboratory, India Specificity and Promiscuity of Phosphoinositide Lipid Interactions with Neuronal GPCRs

16:55 – 17:10

Alina-Maria Halaicu, University of Bucharest, Romania * Lipid-Dependent Dynamics of FGFR3 Transmembrane Dimers

17:10 – 17:25

Nida Yaren Yilmaz, Bogaziçi University, Turkey * Network Model-Driven Molecular Simulations Reveal Allosteric Dynamics and Biased Signaling in Class C GPCRs

17:25 – 17:45

Coffee Break & Posters

Session VI

Signaling Across the Membrane Part II Chair: Valerica Raicu, University of Wisconsin-Milwaukee, USA

17:45 – 18:10

Ching-Ju Tsai, Paul Scherrer Institute, Switzerland Conformational Ensembles of Rhodopsin-G Protein Complexes Reveal Light Perception and GPCR Signaling Mechanisms Jana Selent, Hospital del Mar Research Institute & Pompeu Fabra University, Spain Exploring GPCR Dynamics at Scale Using Molecular Dynamics Simulations

18:10 – 18:35

18:35

Free Time

Wednesday, May 13, 2026

8:30 – 15:00

Registration/Information

Session VII

Receptor Structural Dynamics and Structure-Function Relationships Chair: Kota Katayama, Nagoya Institute of Technology, Japan Keiichi Inoue, The University of Tokyo, Japan Functions and the Photoreaction Dynamics of Non-Canonical Rhodopsins Przemyslaw Nogly, Jagiellonian University in Krakow, Poland Molecular Mechanisms of Photoreceptors Used in Optogenetics by Time-Resolved Crystallography Edina Rosta, University College London, United Kingdom From Correlation to Causation in Molecular Dynamics: Probing Information Transfer in GPCR Ligand Unbinding

9:00 – 9:25

9:25 – 9:50

9:50 – 10:15

10:15 – 10:35

Coffee Break & Posters

Session VIII

Transport in Cells and Across Cell Membranes Chair: Peter Pohl, Johannes Kepler University Linz - JKU, Austria Tomohiro Shima, The University of Tokyo, Japan Writing and Reading the Microtubule Lattice: Biophysical Mechanisms of Cellular Architectural Organization

10:35 – 11:00

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Speaker Abstracts

11:00 – 11:25

Kumiko Hayashi, The University of Tokyo, Japan Force Generation by the Kinesin-3 Family Motor Protein KIF1A and Its Disruption in KIF1A-Associated Neurological Disorder Peter Pohl, Johannes Kepler University Linz - JKU, Austria Light-Controlled Modulation of Neuronal Excitability Using Photoswitchable Lipids Denisa-Sonia Andronic, University of Bucharest, Romania * Molecular Dynamics Simulations of Pore-Forming pHD Peptides

11:25 – 11:50

11:50 – 12:05

12:05 – 13:30

Lunch & Posters

Session IX

Receptor Dynamics and Function Chair: Laurentiu Spiridon, Romanian Academy of Sciences

13:30 – 13:55

Ana-Nicoleta Bondar, University of Bucharest, Romania Dynamic Hydrogen-Bond Networks for G Protein Coupled Receptor Activation Valerica Raicu, University of Wisconsin-Milwaukee, USA 4D Fluorescence Intensity Fluctuation Spectrometry Monitors the Localization and Interactions of Ligand-Activated Muscarinic Acetylcholine Receptors Among Themselves and with Downstream Signaling Effectors Satoshi Tsunoda, Nagoya Institute of Technology, Japan Channelrhodopsins with Defined Biophysical Properties for Optogenetic Control of Neuronal Activity and Vision Restoration

13:55 – 14:20

14:20 – 14:45

14:45 – 15:10

Eric Beitz, University of Kiel, Germany Intrinsic Asymmetry in Monocarboxylate/H+ Transporter Activity

15:10

Free Time

Thursday, May 14, 2026

8:30 – 17:00

Registration/Information

Session X

Drug-Membrane and Drug-Receptor Interactions Chair: Durba Sengupta, CSIR-National Chemical Laboratory, India Kalina Hristova, Johns Hopkins University, USA Biophysics of EphA2 Receptor Signaling in the Membrane

9:00 – 9:25

9:25 – 9:50

Ran Friedman, Linnaeus University, Sweden Lithium, the Mysterious Drug

9:50 – 10:15

Konstantin Mineev, Goethe University Frankfurt, Germany Insights into the Mechanics of Neurotrophin Receptor Signaling from NMR Spectroscopy

10:15 – 10:40

Mariana Pinteala, Romanian Academy of Sciences, Romania Nanoplatforms for Gene Therapy and Bioimaging

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Speaker Abstracts

10:40 – 11:00

Coffee Break & Posters

Session XI

Reactions in Cells and in vivo Chair: Vlad Cojocaru, University of Babes Bolyai Cluj Napoca, Romania

11:00 – 11:25

Joachim Heberle, Freie Universität Berlin, Germany Infrared Nanoscopy for Subcellular Chemical Imaging

11:25 – 11:50

Masha Niv, The Hebrew University of Jerusalem, Israel Hidden Pockets and Intracellular Ions: Lessons from Bitter Taste GPCRs Herbert Nar, Boehringer Ingelheim, Germany Structure, Function and Drug Interactions of Orphan GPCRs Cosmin Trif, Romanian Academy of Sciences, Romania * Something Sweet: A Tale of a Novel Modulator for Free Fatty Acid Receptor (FFAR1/GPR40) Advanced Computational Approaches to Study Membrane Reactions Chair: Andrei Petrescu, Romanian Academy of Sciences, Romania Hossein Batebi, Freie Universität Berlin, Germany Allosteric Communication and Kinetic Regulation in Membrane Proteins Florence Tama, Nagoya University, Japan Seeing Function in Motion: Computational Methods for Protein Dynamics Maria Kurnikova, Carnegie Mellon University, USA Molecular Modeling of the Structure and Function of the Glutamate Receptors Laurentiu Spiridon, Romanian Academy of Sciences, Romania * ROBOSAMPLE: Accelerating Protein Conformational Landscape Exploration via Robot Mechanics Simulations Lunch and Group Photo

11:50 – 12:15

12:15 – 12:30

13:00 – 14:00

Session XII

14:00 – 14:25

14:25 – 14:50

14:50 – 15:15

15:15 – 15:30

15:30 – 16:00

Coffee Break & Posters

Session XIII

Perspectives in Membrane Receptor Dynamics Chair: Gabriela Popescu, University of Buffalo, USA

16:00 – 16:25

Jana Shen, University of Maryland, USA Membrane Crossing of Opioids Revealed by Continuous Constant PH Molecular Dynamics Simulations and Cell Experiments Gebhard Schertler, Paul Scherrer Institute, Switzerland From Structural Studies of GPCRs to Engineering OptoGPCRs as Scientific Tools and for Optogenetic Applications

16:25 – 16:50

16:50 – 17:05

Closing Remarks and Biophysical Journal Poster Awards

17:05 – 18:15

Dinner Buffet and Networking

*Contributed talks selected from among submitted abstracts

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Speaker Abstracts

SPEAKER ABSTRACTS

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Monday Speaker Abstracts

NMDA RECEPTOR: OPERATION AND MODULATORY MECHANISMS Gabriela K Popescu University at Buffalo, SUNY, Biochemistry, Amherst, NY, USA Response to external stimuli and adaptation are two key characteristics of life. In brain, ongoing electrical signal transmission, processing, and integration support moment by moment consciousness, perception, and learning. NMDA receptors are neurotransmitter receptors that respond to the neurotransmitter glutamate by opening an intrinsic transmembrane channel and thus generating a large calcium-rich excitatory current. Blocking this current pharmacologically produces immediate anesthesia and patients with single-residue variations in the primary structure of this neurotransmitter receptor suffer from severe developmental delays, cognitive impairments, and learning deficits. In this lecture, I will describe recent advances in understanding the operation of NMDA receptors and how this knowledge can be leveraged to modulate their stimulus response function for therapeutic gain.

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Monday Speaker Abstracts

SPECTROSCOPIC INSIGHTS INTO THE MOLECULAR MECHANISMS UNDERLYING BIASED GPCR SIGNALING Kota Katayama 1,2 ; 1 Nagoya Institute of Technology, Life Science and Applied Chemistry, Nagoya, Japan 2 Nagoya Institute of Technology, OptoBioTechnology Research Center, Nagoya, Japan Opioid analgesics exert potent pain-relieving effects by activating opioid receptors, a class of G protein–coupled receptors (GPCRs) and remain indispensable for the management of severe pain associated with cancer and other conditions. However, their clinical use is limited by serious adverse effects, including tolerance and dependence. Consequently, there is a strong demand for the rational development of next-generation opioid drugs based on structural and mechanistic insights into opioid receptor signaling, although this effort is challenged by the complexity of receptor-mediated intracellular signaling pathways. Opioid receptor signaling involves at least two major pathways: G protein–mediated and arrestin-mediated signaling. While the former is generally associated with analgesic effects, activation of the latter has been linked to adverse effects, motivating the development of “biased” ligands that selectively modulate specific signaling pathways. Despite extensive efforts, the molecular mechanisms underlying signaling bias in opioid receptors—and GPCRs more broadly—are not yet fully understood. Recent studies have suggested that endogenous sodium ions play a critical role in regulating GPCR signaling bias. Nevertheless, direct observation of sodium ion binding within the receptor has been technically challenging, thereby limiting mechanistic understanding of this phenomenon. In this work, we employ an infrared spectroscopic approach developed in our laboratory to investigate the molecular differences between G protein– and arrestin-mediated signaling pathways in opioid receptors. By measuring ligand- and sodium ion–induced infrared difference spectra of opioid receptors bound to biased agonists and various ligands, we capture subtle changes in molecular interactions that are difficult to detect using conventional structural biology methods alone. In this presentation, we discuss how these spectroscopic signatures provide new insights into the molecular basis of signaling bias in opioid receptors and offer a framework for understanding biased signaling across the GPCR family.

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Monday Speaker Abstracts

REPRESENTATION AND DESIGN IN NETWORK MODELS OF CATEGORY DEFICITS Andrei Ionu ţ M ă r ăş oiu University of Bucharest, Romania No Abstract

SUBTYPE-SPECIFIC CONFORMATIONAL LANDSCAPES GOVERN NMDA RECEPTOR GATING Vasanthi Jayaraman University of Texas Health Science Center at Houston, USA N-methyl-D-aspartate (NMDA) receptors are glutamate- and glycine-gated ion channels that are essential for excitatory neurotransmission, synaptic plasticity, and excitotoxic neuronal injury. Although receptor activation is tightly regulated by co-agonists and modulators, the conformational transitions that give rise to subtype-specific gating and functional diversity remain incompletely understood. Here, we used single-molecule Förster resonance energy transfer (smFRET) to define the conformational landscapes and dynamic transitions of multiple NMDA receptor subtypes, revealing common structural principles that govern activation across distinct GluN1 partner subunits. Across GluN1-containing receptors assembled with GluN2A, GluN2D, or GluN3 subunits, smFRET measurements spanning the amino-terminal domain, ligand-binding domain, and transmembrane domain uncovered subtype-dependent yet mechanistically convergent patterns of domain organization. Receptors with lower open probability preferentially occupied splayed, dynamic extracellular conformations that were associated with more constrained pore configurations, whereas higher open probability states correlated with compact extracellular arrangements and enhanced pore dynamics. Ligands and modulators shifted these equilibria in a consistent manner: agonists or potentiating conditions promoted tighter extracellular domain coupling and coordinated rearrangements in the transmembrane domain consistent with channel opening, while other ligand conditions favored extracellular decoupling and reduced activity. These observations support a unifying “bunch of flowers” model in which coordinated tightening of extracellular domains is coupled to widening of the channel gate to drive activation. Rather than acting through entirely distinct mechanisms, different subunits and modulatory conditions tune receptor function by reshaping a shared conformational landscape. This framework explains how diverse GluN1 partner subunits generate markedly different levels of activity, desensitization, and agonist potency, and provides mechanistic insight into NMDA receptor modulation.

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Tuesday Speaker Abstracts

ML MAPPING OF GPCR INTRACELLULAR POCKET CONFORMATIONS TO MULTIDIMENSIONAL PHARMACOLOGICAL EFFICACY David Minh Illinois Institute of Technology, Chemistry, Chicago, IL, USA We have developed machine learning methods to train models that map from the probability of intracellular pocket conformations observed in molecular simulations of ligand-bound G protein coupled receptors to their efficacy in multiple pharmacological assays. Simulated structures are clustered into conformations that are input into multiple linear regression models. Using fewer than 15 complexes per receptor, we have trained accurate models (mean absolute error of Emax <20%) for CNS-relevant opioid (MOR, DOR, and KOR), 5-HT2A serotonin, and CB2 cannabinoid receptors in transducer recruitment (both G protein subtype and arrestin) and secondary messenger (cAMP) assays. These empirical results suggests a linear proportionality between intracellular pocket conformation probability and signaling efficacy. In addition to outputting multidimensional efficacy, the ML models are highly interpretable as three dimensional structures with features characteristic of GPCR activation including outward motion of transmembrane helices 5 and 6 and rotation of microswitches.

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Tuesday Speaker Abstracts

CLEAVAGE AT THE MEMBRANE: HOW GAMMA-SECRETASE COMPLEX MODULATES NEURONAL COMPLEXITY Maria L Franco; Andrea Benito Martinez; Elena Juarez; Marçal Vilar ; Institute of Biomedicine of Valencia CSIC, Valencia, Spain Loss of basal forebrain cholinergic neurons (BFCNs) is a hallmark of Alzheimer’s disease (AD), yet the processes driving their degeneration are still poorly understood. The neurotrophin receptor p75NTR and the accumulation of amyloid- β (A β ), particularly A β 42, have both been linked to disease progression. We find that increased A β 42 interferes with γ -secretase activity, leading to the buildup of unprocessed protein fragments and activation of p75-dependent neuronal death pathways. In cultured neurons, blocking γ -secretase causes marked changes in BFCN morphology and disrupts synaptic connectivity in hippocampal networks. These effects are eliminated in neurons lacking p75NTR, highlighting its central role. Together, our results suggest that elevated A β 42 contributes to neuronal dysfunction by inhibiting γ -secretase and provide insight into why γ -secretase inhibitors have produced negative cognitive outcomes in clinical studies.

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Tuesday Speaker Abstracts

MEMBRANE PROTEIN ENGINEERING FOR SENSING TRANSIENT MOLECULAR HALLMARKS IN NEURODEGENERATION Devika Vikraman; Liviu Movileanu ; Syracuse University, Department of Physics, Syracuse , NY, USA The seminal discovery of a GGGGCC hexanucleotide repeat expansion in the open reading frame 72 on chromosome 9, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD; C9-ALS/FTD), is a significant advance in neurodegeneration research. Over the past decade, it has been frequently proposed that one mechanism of neuronal damage is the aberrant accumulation of unnatural dipeptide repeat (DPR) proteins in patients' brains in the early stages of the disease. Aggregation of arginine-rich DPR (RDPR) proteins is considered the most toxic. A persistent limitation in further therapeutic development and understanding of ALS/FTD pathologies is the lack of high-resolution technologies for detecting early RDPR cluster formation. In this talk, I will discuss our recent progress in developing a protein nanopore sensing platform for single-molecule detection of RDPR aggregates at their earliest stages, before phase-separating conditions. We recently engineered a single polypeptide chain nanopore that accommodates many negative charges within its lumen. In this way, RDPR monomers and small oligomers can be readily detected through a high-affinity, nonspecific binding mechanism for these intrinsically disordered proteins, which are hallmarks of ALS and FTD. This sensing platform shows promise for further studies to uniquely profile the kinetics and dynamics of RDPR oligomer formation in these pathologies.

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Tuesday Speaker Abstracts

CORRELATING CLATHRIN STRUCTURES WITH ENDOCYTIC DEFECTS IN ALZHEIMER'S DISEASE Lila Gordon 1 ; Justin Taraska 1,2 ; 1 National Institute of Health, NHLBI, Bethesda, DC, USA 2 Brown University, Providence, RI, USA Alzheimer’s Disease causes cognitive decline in millions of people every year. In the 1990s, scientists identified an isoform of the lipid transporter Apolipoprotein E (APOE) that correlates with increased risk of late-onset Alzheimer’s Disease (LOAD). Later, other studies showed that mutations in endocytosis-related genes also correlate with LOAD risk. To synthesize these genetic risk factors, our collaborator showed that cells expressing the LOAD-associated APOE isoform (E4) display functional endocytic defects. One key form of endocytosis is clathrin mediated endocytosis (CME). Through the present collaboration, we aim to explore structural differences in clathrin between disease genotype cells and healthy cells. Astrocytes, the most prevalent cell type in the central nervous system, also produce the most APOE. For this project, we use human iPSC-derived astrocytes. I do platinum replica electron microscopy (PREM) on unroofed cells from the healthy and disease astrocytes. Unroofing allows the user to expose the membrane of cells. Combining this method with PREM allows for the 3D visualization of structures at the membrane. After imaging, I quantify the shapes and sizes of clathrin structures. E4 astrocytes show significantly smaller dome: flat and sphere: dome ratios, which means that highly curved structures occupy a smaller proportion of total structures in those cells. This finding complements the observed reduction in endocytosis, implying that this defect may be clathrin-mediated and is taking place at the plasma membrane. Future directions include identifying structural underpinnings for rescue conditions. The functional data shows that expressing clathrin adaptor proteins rescue the endocytic defect. Additionally, I plan to examine clathrin lifetime for these cells given a probable explanation for an overall comparable amount of clathrin but differences in structure class is clathrin residency time at the membrane. Overall, this method of quantifying structural differences in disease-state versus wild-type presents a landscape of opportunities for examining cellular communication in disease.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

PH-RESPONSIVE PEPTIDE NANOPARTICLES DELIVER MACROMOLECULES TO CELLS VIA ENDOSOMAL MEMBRANE NANOPORATION Eric Wu 1 ; Ace Ellis 1 ; Keynon Bell 2 ; Ana-Nicoleta Bondar 3,4 ; Kalina Hristova 2 ; William C. Wimley 1 ; 1 Tulane University School of Medicine, Biochemistry and Mol. Biol., New Orleans, LA, USA 2 Johns Hopkins University, Materials Science, Baltimore, MD, USA 3 University of Bucharest, Physics, Bucharest, Romania 4 Forschungszentrum Jülich, Institute of Computational Biomedicine, Jülich, Germany The ability to transport proteins and other macromolecular cargos into cells and across cellular barriers remains a significant challenge for therapeutic development. The synthetically evolved pHD family of peptides addresses this challenge through a pH-responsive mechanism that enables membrane permeabilization, but only under acidic conditions. Members of this family self-assemble into macromolecule-sized nanopores (2–10 nm diameter) in lipid bilayers at pH values below ~6. Here, we show that the representative peptide pHD108 exhibits the same pH dependent nanopore-forming activity in the endosomal membranes of living human cells, triggered by endosomal acidification, thereby enabling efficient cytosolic delivery of endocytosed proteins and other large cargos. Addition of acyl groups to either peptide terminus significantly improves delivery efficiency without cytotoxicity. Peptides modified with longer acyl chains are more potent. The most active variant, N-terminally palmitoylated C16-pHD108, delivers diverse macromolecular cargos, including enzymes, fluorescent proteins, and dye labeled dextrans, to the cytosol of human cells. At neutral pH, C16-pHD108 assembles into stable, monodisperse micellar nanoparticles (~30 nm diameter) that are non-lytic and non-toxic. Acidification destabilizes these nanoparticles and promotes membrane binding and nanopore formation. These results support a delivery mechanism in which passive uptake of cargo and peptide nanoparticles is followed by acidification-triggered activation of nanoporation in endosomal membranes, enabling macromolecular cargo to escape into the cytosol. This system provides a general platform for intracellular and trans-barrier delivery of large biological cargos, with potential relevance to challenging targets such as the blood–brain barrier.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

MEMBRANE TOPOGRAPHY VARIATIONS AND QUANTITATIVE BIOLOGY - PITFALLS AND SOLUTIONS Ingela Parmryd Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden To understand complex cellular processes in the plasma membrane, quantitation is essential. For the data interpretation to generate biological insights we need to acknowledge that across a range of length scales the plasma membrane is not flat. However, uncovering high-resolution membrane topography is very challenging and its importance is therefore frequently dismissed or ignored. In single particle tracking, movement is recorded with high lateral and temporal resolution, but the z-dimension is often absent. Simulations of Brownian motion on surfaces with pillars ridges, with movement in three dimensions but only recorded in two, consistently underreports the diffusion rates and can be misinterpreted as transient confinement or anomalous diffusion (PMID:20195248). Importantly, even 3D Euclidean distance measurements substantially underreport diffusion on non-flat surfaces because it is essential that membrane molecules remain in the membrane. The shortest within surface (geodesic) distance, is a solution for foldable but not deformed (unfoldable) surfaces because topographical features themselves can produce the appearance of anomalous diffusion (PMID:30652124). Membrane topography variations are not homogeneously distributed being smaller above the nucleus than other parts of the cell. Failing to appreciate this can mislead the interpretation of fluorescence correlation spectroscopy data and a remedy is to account for the amount of membrane in the detection volume using a membrane marker (PMID:32903922). Single-molecule localisation microscopy suggests that most plasma membrane proteins are organised in clusters but local membrane density differences exist and will make randomly distributed membrane molecules appear clustered. Differentiation between genuine and topography-variation-caused clusters requires including a membrane marker to map the local amount of membrane (PMID:38951588). Our findings suggest that clustering and non-Brownian motion are less common than the contemporary literature implies. In conclusion, acknowledging membrane topography radically improves the interpretation of experimental data and of the underlying biology.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

MITOCHONDRIAL UNCOUPLING PROTEIN 4 IN BRAIN: PUTATIVE FUNCTIONS AND MOLECULAR MECHANISMS. Elena E. Pohl University of Veterinary Medicine, Medical Physics and Biophysics, Vienna, Austria Uncoupling Protein 4 (UCP4) is a neuron-specific member of the mitochondrial carrier superfamily SLC25. In contrast to UCP1, whose thermogenic function in brown adipose tissue is well characterized, UCP4 exhibits a distinct functional profile, playing an important role in regulating cellular energy metabolism and protecting against oxidative stress. In neuronal model systems, increased UCP4 expression leads to a reduction in mitochondrial calcium overload and improves cell survival rates under stress conditions. While UCP2 is more commonly found in proliferative, glycolytic stem cells, UCP4 expression increases significantly during neuronal differentiation, suggesting a specialization for postmitotic neurons. Functionally, UCP4 is associated with the modulation of the mitochondrial membrane potential by transporting protons in the presence of long-chain fatty acids. However, the transport of metabolites has also been hypothesized, suggesting a dual function of the protein. In conclusion I will discuss the AI-based structure of UCP4 and the putative molecular mechanism of its proton transport.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

ILLUMINATING NEUROSECRETION: OPTOGENETIC AND CLICK CHEMISTRY NOVEL TOOLS TO HIGHLIGHT THE MULTIPLE ROLES OF PHOSPHATIDIC ACID IN NEUROTRANSMITTER RELEASE Nicolas Vitale Institut for Cellular and Molecular Integrated Neurosciences, CNRS UPR3212, Strasbourg, France The orchestrated release of neurotransmitters or hormones by secretory cells involves many vesicular trafficking steps for efficient and rapid release. In addition to key proteins, the contribution of lipids in these various steps along the secretory pathway has been recently postulated. Among them, phosphatidic acid (PA), the simplest glycerophospholipid, has been proposed to play pivotal roles in key trafficking steps, especially in membrane fusion and fission events, where lipid remodeling is deemed crucial. For instance, using genetic knockdown, pharmacological inhibition of PA-producing enzymes, and PA sensors, we have highlighted the diverse contribution of this phospholipid across multiple stages of neurosecretion. Furthermore, lipidomic analysis of fractionated membranes has revealed the widespread presence of PA in numerous subcellular compartments and its active modulation during cellular stimulation. This sheds light on the complexity of PA signaling, with the existence of different PA pools defined not only in space, but also in time. However, establishing a functional link between these pools and the multiple functions attributed to PA has remained impossible using currently available tools. Hence, to overcome both spatial and temporal limitations, we developed a novel optogenetic strategy targeting lipid metabolism to specific organelles and new PA clickable PA analogues. Hence, using light sensible PA metabolism enzymes to induce recruitment at specific subcellular membranes, we achieved by the minute modulation of PA levels within specific compartments. This precise control of PA levels coupled with confocal imaging to monitor exocytic sites enabled us, for the first time, to establish insights into the distinct pools of PA involved in specific steps of the secretory pathway. Furthermore, to preserve the biological properties of PA synthetic analogues, we developed a novel strategy for the synthesis of azide based analogues allowing specific fatty acyl chain positioning. After functional validation of mono and poly-unsaturated forms of PA analogues in bovine chromaffin cells, we characterized their functional interactome during neurosecretion leading to the identification of known PA interactors involved in exocytosis and many additional potential novel interactors. Altogether, these results validate the versality of these tools to study the biological activities of PA and could be extended to other glycerophopsholipids.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

DIFFERENTIAL OXYTOCIN RECEPTOR SIGNALING DRIVES THE REVERSAL OF SOCIAL TRAUMA-INDUCED AVOIDANCE IN MICE Rohit Menon University of Regensburg, Department of Behavioral and Molecular Neurobiology, Regensburg, Germany Successfully navigating social situations is an essential survival skill for mammals. Oxytocin (OXT) signaling in the lateral septum (LS) is a critical regulator of social behavior, but its underlying neural mechanisms remain poorly understood. In our study, we leverage the operant conditioning-based social fear conditioning paradigm to examine the role of OXT signaling in the LS in regulating recovery from social trauma. First, we show that OXT receptor (OXTR)- expressing neurons are enriched in the caudal LS (LSc) and exhibit pronounced activation during social interaction in the extinction phase following social fear acquisition (i.e., social trauma), indicating that the valence of the social stimulus is critical for activating the OXTR-expressing LS neurons (LS OXTR ). A temporally precise analysis of LS OXTR activity revealed their heightened inhibition at the exact timepoint of social interaction in mice with successful extinction (Responders: Res), while such modulation is absent in mice with unsuccessful extinction (Non responders: Nres). Interestingly, LS OXTR neurons of NRes mice are activated right after social fear extinction in comparison to the Res mice. In all mice, chemogenetic inhibition of LS OXTR disrupts social fear extinction, whereas optogenetic stimulation has no effect, suggesting that the abovementioned temporal modulation is essential for successful extinction. Moreover, pharmacological activation of OXT signaling using synthetic OXT, TGOT (a complete OXTR agonist), or atosiban (a selective OXTR-Gi agonist) facilitates extinction of social fear. These findings indicate that precise temporal inhibition of LS OXTR activity driven by OXTR-coupled Gi signaling is critical for adaptive social behavior, positioning OXT signaling in the LS as a key calibrator of social valence.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

MOLECULAR PHYSIOLOGY OF VESICULAR GLUTAMATE TRANSPORTERS Christoph Fahlke ; Victor Lugo Forschungszentrum Juelich, Molecular and Cell Physiology, Juelich, Germany Vesicular glutamate transporters accumulate glutamate in synaptic vesicles, where they also function as Cl- efflux pathway to permit osmotically neutral neurotransmitter accumulation. We combined cellular electrophysiology with mathematical modeling to describe this dual function in rat as well as in Drosophila melanogaster VGLUT. Rat VGLUT1 functions as stoichiometrically coupled H+-glutamate exchanger, with a transport rate of around 600 s-1 at - 160 mV. Transport of other large anions, including aspartate, is not stoichiometrically coupled to H+ transport, and Cl- permeates VGLUT1 through an aqueous anion channel with unitary transport rates of 1.5 × 105 s-1 at -160 mV. DVGLUT and rVGLUT1 closely resemble in glutamate transport. In both, luminal Cl- is necessary as allosteric activator, however, the allosteric affinity is higher in fly than in rat transporters. DVGLUT anion channels exhibit lower unitary currents, but higher anion channel open probabilities, resulting in larger Cl- currents for the fly transporter in the presence of cytoplasmic glutamate. The higher allosteric affinity together with the enhanced anion channel activity may serve as evolutionary adaptation of VGLUTs to lower ion concentrations in Drosophila, illustrating the impact of these particular features for synaptic vesicle filling.

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Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

LIPID NANOTUBES AS A MODEL SYSTEM FOR NEURON SIGNALING AND MORPHOLOGICAL PLASTICITY Jan Steinkühler Kiel University, Bio-Inspired Computation, Kiel, Germany Voltage-sensitive ion channels stand at the centre of studies of cellular excitability in neuronal networks. However, the spatial propagation of electrical waves along nerve fibres is not a property inherent to an individual ion channel but rather emerges from the arrangement of ion channels along a tubular lipid membrane. While the in-vitro study of functional ion channels in model membranes is well established, the propagation of an action potential along a lipid-bilayer nanotube has not yet been studied. Here, we present our experimental work investigating these phenomena using electrical and optical measurements on force-induced lipid nanotubes pulled from giant unilamellar vesicles (GUVs) and demonstrate the cable-like properties of such nanotubes. Furthermore, we study memory effects arising from the interplay between electrically induced lipid migration and ionic nanochannel conductance. Based on these measurements, we develop a new hypotheses of membrane-based plasticity that shed light on recent findings of a syncytial nerve net in ctenophores, emphasizing the role of membrane morphologies in the evolutionary origins of nerve nets. Finally, we present our lab’s efforts toward automated cell free expression of ion channels and data-driven modelling of membrane excitability. More broadly, our results help establish the interplay between membrane phase, shape, and electrical properties in a controlled biophysical experimental setup.

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