Sarah Veatch

Sarah Veatch

Assistant Professor of Biophysics and Physics

Ph.D., University of Washington
Postdoctoral Fellow, Cornell University and University of British Columbia

Research Focus: Physical properties of plasma membrane lipids

Phone: 734.615.2099
E-mail: sveatch@umich.edu

My multi-disciplinary research program aims to understand how the physical properties of lipids and lipid mixtures influence lateral organization, protein interactions, and functional processes at the plasma membrane of mammalian cells. It is increasingly recognized that functional heterogeneity in cell plasma membranes arises, at least in part, from the tendency for lipid mixtures to demix into two distinct liquid phases, called liquid-disordered and liquid-ordered. My laboratory aims to decipher the ways in which the mixing properties of lipids contribute to biological processes and to develop methods to manipulate these biological processes using the tools of physical chemistry and chemical biology.

The bulk of my research program is guided by the working hypothesis that cell plasma membranes are poised in the vicinity of a miscibility critical point, and that long range and dynamic critical fluctuations occur in intact plasma membranes at physiological temperatures. This is supported by our recent observations of large and dynamic composition fluctuations in purified model membranes and isolated plasma membrane vesicles that have been detached from cortical cytoskeleton. Our research effort focuses in four complimentary areas that span the fields of physical chemistry to cell biology:

1. We use theoretical models of critical systems to explore the effects of lipid heterogeneity in different biological contexts, such as when fluctuating membranes are coupled to cortical actin or when receptors redistribute upon ligand binding. By exploring the consequences of criticality through simulations and analytical modeling, we develop predictions regarding the organization and mobility of membrane components that can be tested experimentally.

2. We conduct experiments using purified model membranes to demonstrate consequences of criticality, such as when model membranes are coupled to a reconstituted actin cortex, or when the distribution of membrane components is modulated through adhesion or multivalent binding. These experiments validate and refine theoretical predictions, and enable the development of quantitative methods to investigate membrane-mediated organization in complex cellular systems.

3. We investigate membrane heterogeneity and dynamics in intact cells using super-resolution localization microscopy, as predicted structures arising from lipid-mediated lateral organization is both small and subtle. Our experimental strategy is guided by results in model systems and probes proteins and lipids in chemically fixed and living cells. We also quantify stimulated responses for functional processes where membrane lipids are known to play an important role, such as receptor redistribution during immune signaling in B and T cells. Through quantitative predictions and experiments, we aim to test our working hypothesis that critical fluctuations form the physical basis of lipid-mediated membrane heterogeneity in cells.

4. We use biochemical perturbations to manipulate membrane fluctuations and physical properties in cells and monitor functional outcomes. Through experiments in purified model membranes and isolated plasma membrane vesicles, we characterize chemical treatments that modulate membrane fluctuations and transition temperatures. In parallel, we probe membrane organization and functional outcomes in cells exposed to the same chemical treatments. Through this Chemical Biology approach, we aim to develop methods to better characterize and control the roles of lipids in a wide range of normal cell processes and disease states.



ISSFAL Young Investigator Award

Representative Publications

  1. S. L. Veatch, P. Cicuta, P. Sengupta, A. Honerkamp-Smith, D. Holowka, B. Baird "Critical Fluctuations in Plasma Membrane Vesicles", ACS Chem. Bio. 3, 287-293 (2008).

  2. S. L. Veatch, O. Soubias, S. L. Keller, and K. Gawrisch "Critical fluctuations in domain forming lipid mixtures", Proc Nat Acad Sci USA 104 17650-17655 (2007)

  3. S. L. Veatch, K. Gawrisch, and S. L. Keller "Closed-loop miscibility gap and quantitative tie-lines in ternary membranes containing diphytanoyl PC", Biophys J. 90(12) 4428-36 (2006).

  4. S. L. Veatch and S. L. Keller "Seeing Spots: Complex Phase Behavior in Simple Membrane", Biophys. Acta. 1746 172-85 (2005).