Membrane Recognition & Binding to Control Biological Processes

The Challenge

The membrane protects the cell from the outside world and is an important site for catalysis and signaling. It is also regularly attacked by pathogens. Investigators in the membrane recognition and binding thrust address the challenges of understanding how proteins and engineered molecules and materials recognize their targets within a membrane and how the membrane system responds and restructures as a result of binding events.

The Innovation/Technology

A holistic approach to interactions between soluble biomolecules and membranes: from design and fabrication to measuring mechanical properties to molecular characterization.

The Impact

Understanding how biomolecules and nanoparticles manipulate membranes will facilitate the design of new therapies aimed at disrupting molecule-membrane interactions. These insights may also assist in the design of new materials with readily manipulatable shapes and physical properties.

The Solution

The UMass investigators bring together a host of tools and strategies to study membrane recognition and response from the inter- and intra-molecular to the whole cell level. Membrane binding, whether to lipids or membrane proteins, couples with other membrane processes including response to tension and phase transitions. Model systems and methods from fluorescence spectroscopy and advanced microscopies to tension manipulation and study of membrane mechanics address the complexity and interplay between these behaviors. With these systems, UMass investigators have elucidated the energetic and kinetic aspects of binding in addition to important interfacial behaviors coupled to binding. These include specificity due to lipid headgroup recognition, changes in line tension around raft-like phase separate domains in response to protein binding, heterogeneous particle behavior (modeling viruses and bacteria), and the impact of tension on phase separated membrane domains.

Chen, D., and Santore, M. M. Large effect of membrane tension on the fluid-solid phase transitions of two-component phosphatidylcholine vesicles. Proc Natl Acad Sci USA 111, 179–184 (2014).
Gao Y. and Kilfoil, M.L. Intermittent and spatially heterogenous single-particle dynamics close to colloidal gelation. Phys Rev E 79, 051406 (2009).
Grauffel, C., Yang, B., He, T., Roberts, M. F., Gershenson, A., and Reuter, N. Cation-π interactions as lipid-specific anchors for phosphatidylinositol-specific phospholipase-C. J Am Chem Soc 135, 5740–5750 (2013).
Gurnev, P.A., Yap, T.L, Pfefferkorn,C.M., Tatiana K. Rostovtseva, T.K., Berezhkovskii, A.M., Lee, J.C., Parsegian,V.A.and Bezrukov,S.M. Alpha-Synuclein Lipid-Dependent Membrane Binding and Translocation through the α-Hemolysin Channel, Biophys J 106, 556-565 (2014).
Hutchison, J. B., Weis, R. M., and Dinsmore, A. D. Change of line tension in phase-separated vesicles upon protein binding. Langmuir 28, 5176–5181 (2012).
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