Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Tuesday Speaker Abstracts

LIPID-DEPENDENT DYNAMICS OF FGFR3 TRANSMEMBRANE DIMERS Alina-Maria Halaicu 1 ; Kalina Hristova 2 ; Ana-Nicoleta Bondar 3,4 ; 1 Faculty of Physics, University of Bucharest, Experimental and Computational Physics, Medical Physics, Bucharest, Romania 2 Johns Hopkins University, Department of Materials Science and Engineering, Institute for NanoBio Technology, Baltimore, MD, USA 3 Faculty of Physics, University of Bucharest, Electricity, Solid Physics and Biophysics, Bucharest, Romania 4 Forschungszentrum Jülich , Institute of Computational Biomedicine (IAS-5/INM-9), Jülich, Germany Receptor tyrosine kinases (RTKs) control and regulate cell growth and differentiation and are involved in many human neurological and oncological pathologies. RTKs are type I membrane proteins that create intracellular signalling cascades in response to ligand binding. The signal transduction of RTKs involves ligand-induced receptor dimerization, followed by autophosphorylation of the intracellular kinase domains. This process sets into motion a series of intracellular protein–protein interactions, ultimately propagating signals to proteins that regulate gene transcription. Despite many years of research, the mechanism by which signals are transmitted across the membrane, and how membrane properties influence RTK activation, remain unclear. The objective of this study is to determine and understand how lipid membrane composition influences the conformational dynamics of RTK transmembrane and intracellular kinase domains, using fibroblast growth factor receptors (FGFRs) as model systems. Atomistic molecular dynamics simulations were performed on FGFR3 transmembrane dimers in hydrated phosphatidylcholine (POPC, DOPC), phosphatidylethanolamine (DOPE), and phosphatidylserine (DOPS) bilayers. Several distinct initial dimer conformations were simulated to evaluate lipid-dependent effects. Our results show that lipid composition significantly influences RTK transmembrane dimer stability and orientation. DOPE and DOPS membranes promote protein–lipid hydrogen bonding and helix tilt fluctuations, while locally altering bilayer thickness relative to phosphatidylcholine membranes. The authors gratefully acknowledge computing time on the supercomputer JURECA at the Forschungszentrum Jülich under grants no. DYNAMICNETWORKS and PHDPORES.

27