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BIOPHYSICAL GLYCOSCIENCE

The glycocalyx is a polymer meshwork comprised of proteins and complex sugar chains called glycans. From a physical perspective, the glycocalyx has long been considered a simple “slime” that protects cells from mechanical disruption or against pathogen interactions, but the dramatic complexity of the structure argues for the evolution of more advanced functionality. The overarching hypothesis of our lab is that the glycocalyx, along with its embedded signaling systems, evolved to enable and regulate advanced forms of intercellular communication. Multicellular life must continually answer the question of who receives what information at what time, from where, and how. Our lab seeks to address what role the glycocalyx plays in packaging, sending, and receiving biomolecular information through intercellular communication protocols.

Our recent report in Cell describes a breakthrough in deciphering how the glycocalyx regulates curved membrane features that are known to play major roles in communication (read more >).  Cells project fine membrane extensions and bud off tiny membrane vesicles to transfer messages to other cells.  Combining new theory and experiment, we’ve learned that cells can bend their membranes into these curved forms through assembly of membrane-anchored biopolymers in the cellular glycocalyx.  Like a compressed gas hovering over the membrane, flexible glycocalyx polymers generate a pressure that makes the formation of curved membrane features easier. In an important achievement, we recently published a theory for the coupled mechanics of the glycocalyx and the cell membrane.  Our theory carefully considers contributions of biopolymer elasticity, excluded volumes, entropic terms related to counterion mobility, and other physical interactions (read more >).

Ongoing work seeks to understand the physical principles that underlie molecular organization within the glycocalyx.  We take an integrated approach that combines our genetic approaches for glycocalyx engineering with advanced optical imaging and cell biology.

The Shapes of Intercellular Communication

The beautiful electron micrographs (credit: Dr. Joe Kuo) show cells programmed to synthesize varying amounts of mucin biopolymer in their glycocalyx. Cells interact and communicate with other cells and their environment differently depending on their surface shapes.

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