Hassel and Marianne Ledbetter MatSE Colloquium - "Sensing and Shaping Biological Membranes through Protein-Lipid Interactions"

Cellular membranes are dynamic interfaces that regulate communication, trafficking, and molecular uptake. Understanding how proteins sense and remodel these interfaces is central to explaining cell function and to designing new delivery strategies.

My research group integrates engineering principles with quantitative fluorescence approaches to uncover the physical mechanisms that govern protein–membrane interactions. In this seminar, I will highlight our work across several protein–membrane systems. We examine how the intrinsically disordered protein α-synuclein, which is implicated in Parkinson’s disease, modulates its membrane binding through post-translational modifications and drives membrane curvature.

We also investigate how clathrin assembles on membranes, both independently and in concert with adaptor proteins, to promote endocytic membrane fission. In parallel, we study cell-penetrating peptides that exhibit a striking ability to undergo directional transport across membranes, leading to accumulation within vesicles and cells.

Finally, we explore engineering strategies that couple membrane-active peptides to molecular cargo to enhance cellular uptake. Together, these studies define general physical principles by which proteins sense and shape biological membranes, providing a framework for understanding membrane remodeling, regulation of cellular surfaces, and the rational design of intracellular delivery systems.