Biophysical Society Bulletin | July-August 2024

Publications

Know the Editor María García-Parajo

Editor's Pick

(a)

including OFF state k 1

original Land (2017) model

Barcelona Institute of Science and Technology Editor, Cell Biophysics Biophysical Journal

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C K ×/÷ (1+ k force F ) k 2 k 1 ×/÷ (1+ k force F ) k 2

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Ca 2+

María García-Parajo

Trpn Ca 2+

What are you currently working on that excites you? Biomolecular interactions in living cells are highly coordinat ed in space and time, with modularity playing a major role in tuning molecular function and cell response. We are interested in understanding the rules that govern modularity and spatio temporal compartmentalization to regulate cellular function. For this, we develop and apply a battery of single-molecule fluorescence-based techniques that include different forms of super-resolution microscopy combined with single-molecule imaging and tracking in living cells. We focus on two main bio logical processes of fundamental interest: plasma membrane organization and intracellular dynamics and transport. These processes are sensitive to the mechanical environment, and we aim to understand how mechanical stimuli are sensed at the level of individual molecules, how they influence the modularity and spatiotemporal compartmentalization of molecules, and how this affects cellular function. At a cocktail party of non-scientists, how would you explain what you do? Individual molecules in living cells are similar to individual per sons in our society. Each of us has a defined personality. How ever, we don't function in an isolated manner, but instead we interact with others, and these interactions ultimately define particular functions: from being a parent and a partner to hav ing a given job or providing service to our community. Impor tantly, we are not only parents or professionals: we diversify our functions by interacting with others depending on the place where we are (spatial compartments) and for a given time (dynamics). In our research, we engineer highly sophisticated microscopes with extreme sensitivity to spy on the behavior of thousands of individual molecules to reconstruct cell function from their dynamic interactions.

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Biophysical Journal Cardiac length-dependent activation driven by force-depen dent thick-filament dynamics Alexandre Lewalle, Gregory Milburn, Kenneth S. Campbell, and Steven A. Niederer “The mechanistic origins of length-dependent activation (LDA), a fundamental regulatory feature of cardiac muscle contraction, are still debated. Growing experimental evidence suggests that myosin crossbridges transition between a tension-generating 'on' state and an inactive 'off' state in a tension-dependent manner. Using a minimal biophysical model, the authors tested the hypothesis that the resulting feedback effect could potentially constitute a major contri bution to LDA. By assuming a force-dependent feedback, the model quantitatively reproduces the key features of LDA. It also reproduces qualitatively the main observed effects of the off-state-targeting drug mavacamten. This provides a modeling framework for investigating the impact of off-state dynamics on whole-heart physiology and its clinical implica tions.” Version of Record Published May 27, 2024 DOI: https:/doi.org/10.1016/j.bpj.2024.05.025 F active F passive F F 1 F 2 F d

July/August 2024

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