Biophysical Society Thematic Meeting | Riga 2026

Active and Responsive Soft Matter: From Biological to Engineered Systems

Tuesday Speaker Abstracts

UNRAVELING THE ROLE OF VIMENTIN IN CELL MIGRATION Alison Patteson 1 ; 1 Syracuse University, Syracuse, New York, USA

No Abstract

ACTIVELY DRIVEN LIPID ASYMMETRY CREATES UNIQUE PLASMA MEMBRANE PROPERTIES Kandice R. Levental 1 ; Milka Doktorova 2 ; Ilya Levental 1 ; 1 University of Virginia, Molecular Physiology and Biophysics, Charlottesville, VA, USA 2 Stockholm University, Department of Biochemistry and Biophysics, Solna, Sweden The plasma membrane is the interface between the external world and a cell’s internal chemistry, and must therefore facilitate a multitude of parallel, tightly regulated tasks. To achieve this functional complexity, mammalian cells produce hundreds of lipid species, nearly all of which are actively asymmetrically distributed between the two leaflets of the plasma membrane bilayer. Using quantitative lipidomics we determined the asymmetric distribution of all phospholipids in human erythrocyte plasma membranes. In addition to defining the asymmetric lipidomes of the two PM leaflets, we discovered that the cytoplasmic leaflet contains ~50% more phospholipids than the exoplasmic leaflet. We show that this imbalance of phospholipids in the plasma membrane is enabled by the large abundance of cholesterol (~40%) in the plasma membrane, which can rapidly flip between leaflets to buffer area and mechanical stresses. Through computational and experimental approaches, we find that the combination of cholesterol’s preference for the more saturated exoplasmic lipids and the overabundance of lipids in the cytoplasmic leaflet yields a major enrichment of cholesterol in the exoplasmic leaflet. We show that this out-of-equilibrium distribution can be manipulated by changing the determinants of cholesterol asymmetry, namely the disparity in phospholipid composition and abundance between leaflets. Addition of phospholipids to the outer leaflet redistributes cholesterol to the cytosolic leaflet of the plasma membrane, leading to cholesterol’s recognition by cytoplasmic sensor proteins (i.e. GRAMD), which transfer it to the endoplasmic reticulum for esterification into cholesterol esters and storage in lipid droplets. Thus, active transbilayer asymmetry is a central determinant of cellular lipid homeostasis.

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