The Sweet Side of Mechanobiology: The Glycocalyx Mechanically Regulates Receptor Function at the Nanoscale

Friday, January 18, 2013 - 2:00pm
Fung Auditorium | Powell-Focht Bioengineering Hall
Matthew Pascek, Ph.D

Kavli Fellow, Laboratory for Atomic and Solid State Physics
Cornell University

The Sweet Side of Mechanobiology: The Glycocalyx Mechanically Regulates Receptor Function at the Nanoscale

Abstract: 
Mechanical perturbations to cell and tissue structures are now recognized to contribute directly to disease processes, leading to the emergence of interest in therapeutic approaches that target the biophysical basis of disease. For example, I demonstrate that tissue stiffening and enhanced cell contractility drive a metastatic cancer phenotype, which can be reversed by pharmacologically targeting the pathway controlling cellular force generation. These studies foreshadow improvements in human health stemming from a greater understanding of how cells physically interact with their environment and how these interactions inform cellular decision-making through the process of mechanotransduction. While almost all contemporary studies of mechanobiology have focused on proteins, correlations of altered cell surface glycosylation with disease abound, including with cancer. Cell-surface glycans and glyco-proteins collectively form the glycocalyx, a structure with bulk physical properties that can influence extracellular interactions. Owing to these physical properties and their location on the cell surface, glycans are in prime position to physically and spatially orchestrate the flow of environmental information into signal transduction networks. To investigate how cell surface carbohydrates spatially control biological processes occurring at or near the plasma membrane, I discuss the development of Scanning Angle Interference Microscopy. This new approach permits the inner workings of cellular machines to be imaged dynamically at the nanoscale. Using SAIM along with a combination of imaging, molecular, and computational approaches, I discuss how the cellular glycocalyx is a mechanical regulator of integrin-mediated sensory processes. Together, my results demonstrate a novel mechanism through which integrin signaling is mechanically misregulated in cancer.
Bio: 

Dr. Paszek studied chemical engineering and biology as an undergraduate at Cornell University. He continued his graduate studies in bioengineering at the University of Pennsylvania, where he investigated the mechanobiology of cancer under the mentorship of Drs. Daniel Hammer and Valerie Weaver. Dr. Paszek expanded on his graduate studies as a Postdoctoral fellow with Dr. Weaver, during which time he developed new methods for nanoscale cellular imaging and identified the glycocalyx as a novel mechanical regulator of cancer cell biology. Dr. Paszek is currently a Fellow at the Kavli Institute for Nanoscale Science at Cornell University, where he is developing new tools for the nanoscale investigation of cell surface glycan function.