Ligand Binding and Transport Dynamics on the Cell Surface Ecosystem
ONLINE CBE SEMINAR
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Speaker
Sho Takatori, Ph.D.
Assistant Professor
Dept. of Chemical Engineering
University of California, Santa Barbara
Abstract
The plasma membrane of mammalian cells is now understood to be a highly complex surface. Mass spectrometry, microscopy, and bioinformatics have revealed great diversity in size, composition, and post-translational modifications of cell surface proteins. Collectively called the “glycocalyx”, the dense coating of membrane proteins and glycans covering the cell surface is known to be important for biochemical signaling but its ability to modulate physical interactions with soluble molecules and other cells is unknown. Here we demonstrate that physical crowding of the cell surface glycocalyx directly modulates the binding of soluble macromolecules to the plasma membrane. We introduce a set of molecular probes and use their binding isotherm to make a direct calculation of the in-plane osmotic pressure resulting from surface crowding. We show that osmotic pressure reduces the binding affinity of an IgG antibody to the surface, by up to a factor of ~7x, meaning that affinity is context dependent. Surprisingly, we found that surface charges contributed by sialic acids, a negatively-charged monosaccharide, increase cell surface osmotic pressure far more than molecular weight or number density, accounting for ~50% of the reduction in IgG affinity for red blood cells. Guided by statistical mechanics theory and molecular dynamics simulations, we highlight the impact of cell surface crowding on ligand binding and transport, as well as the formation of cell-cell interfaces.
BIO
Sho Takatori is an assistant professor in the Department of Chemical Engineering at UCSB since March 2020. His research group focuses on advancing the basic fundamental understanding of biological soft materials, including bacterial biofilms, cell membrane interfaces, and colloidal suspensions with tunable bio-interfaces. Before starting his independent position, Sho Takatori was a Miller Research Fellow at UC Berkeley in the Bioengineering Department. He obtained a PhD in Chemical Engineering at Caltech working on the fluid dynamics and rheology of nonequilibrium active matter systems. Prior to Caltech, Sho Takatori earned a bachelors in Chemical Engineering from UC Berkeley.
