Biophysical Society Conference | Tahoe 2024

Molecular Biophysics of Membranes

Thursday Speaker Abstracts

IMMUNE RECEPTOR SIGNALING DOMAINS ARISE FROM A RESPONSIVE PLASMA MEMBRANE Sarah A. Shelby 1 ; Sarah L Veatch 2 ; 1 University of Tennessee, Biochemistry & Cell and Molecular Biology, Knoxville, TN, USA 2 University of Michigan, Biophysics, Ann Arbor, MI, USA Long-standing evidence supports a role for plasma membrane heterogeneity in modulating interactions of immune receptors such as the B cell receptor with its signaling partners, suggesting that membrane domains participate in the regulation of B cell receptor activation. Our recent work uses super-resolution microscopy to directly visualize membrane domains that arise upon B cell receptor clustering on the surface of intact, live cells. This approach enables a quantitative comparison of protein partitioning in cellular domains and phase-separated domains in isolated model membrane vesicles. Our results point to membrane phase separation as a physical driver of membrane domain formation in cells, with implications for receptor signaling output. We propose a model in which membrane organization is responsive, where domains are easily induced upon assembly of receptor complexes because the thermodynamic state of the membrane is poised near a miscibility phase transition. Our ongoing work is applying these concepts to predict and manipulate signaling in engineered immunoreceptor systems.

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