Title:

Flexible protein networks in membrane mechanics and medicine

Speaker:

Dr. Jeanne Stachowiak

Affiliation:

The University of Texas at Austin

When:

Wednesday, November 9, 2022 at 11:00:00 AM   Add to Calendar

Where:

GTMI Building, Room Auditorium

Host:

Dr. Ankur Singh
ankur.singh@me.gatech.edu

Abstract

As the gateway for cellular entry and communication, the surface of the cell holds the answers to critical questions in biology and medicine, while simultaneously providing inspiration for engineered materials and systems. What captivates me about membranes is their ability to precisely and rapidly organize themselves in an environment of staggering complexity. Thousands of distinct protein species reside on cellular membranes, yet functional lipid-protein complexes can form within seconds in response to diverse stimuli. How is this possible? The established view is that highly structured protein complexes are responsible for organizing membranes. However, my lab and others are revealing the critical role of flexible, transient protein networks in orchestrating biological events at membrane surfaces. As one example, our recent work has shown that short-lived assemblies of disordered proteins, which have liquid-like properties at bulk scale, provide an optimal catalytic platform for assembly of endocytic vesicles, which are responsible for cellular uptake of receptors, drugs, and pathogens. In particular, we found that the early initiator proteins of clathrin-mediated endocytosis form a flexible network that permits the dynamic rearrangement of proteins and lipids required for membrane budding. As the structured clathrin coat is recruited, the transient complex of initiator proteins is progressively excluded from the budding vesicle, such that it remains at the cell surface to catalyze future rounds of endocytosis. This understanding provides new insight into the optimal design of therapeutic carriers that harness endocytosis for entry into cells. Specifically, we found that therapeutic nanoparticles must bind to cellular receptors tightly enough to localize to the cell surface but not so tightly that they disrupt the dynamic protein network responsible for endocytosis. More broadly, our lab seeks to understand and mimic the ability of biological membranes to spontaneously reorganize in response to diverse cues. This remarkable capacity for self-organization, which is largely absent in man-made materials, holds great promise for the design of responsive, cell-like therapeutic systems.

Biography

Dr. Jeanne Stachowiak received a doctorate in Mechanical Engineering from the University of California, Berkeley in 2008, under the supervision of Professor Daniel Fletcher. She then served as an independent Staff Scientist at Sandia National Laboratories, where her research program explored basic biophysical questions and practical applications of lipid membrane materials and systems. Dr. Stachowiak has been a faculty member in the Department of Biomedical Engineering at the University of Texas at Austin since 2012, receiving the NSF CAREER Award in 2014. Through quantitative molecular-scale measurements and the design of biomimetic materials, her research program aims to elucidate the physical basis of cellular membrane organization and to design biologically-inspired materials and systems for biomedical applications. In 2022 she was elected a Fellow of the American Institute of Medical and Biological Engineering and received the Michael and Kate Barany Award for Young Investigators from the Biophysical Society. She currently serves on the Editorial Board of the Biophysical Journal and Science Advances.

Notes

Refreshments will be served.