Cellular membranes are critical interfaces for the biochemical interactions that regulate cell behavior and function. These membranes are composed of heterogeneous mixtures of lipids and proteins. Understanding and controlling biomolecular interactions that occur at membranes is challenging owing to the inherent ability of the membrane environment to functionally couple interactions between proteins and lipids. Nonetheless, elucidating the interplay between proteins and lipids in biological membranes is important for a variety of applications, such as pinpointing the mechanisms of disease, discovering and delivering new drugs, and developing functional biomaterials. Toward addressing these challenges, our group uses engineering principles and fluorescence techniques to develop the tools, approaches, and ideas that will enable us to understand and control the protein-lipid interface.

This presentation will primarily focus on protein-lipid interactions that facilitate sensing and/or generation of membrane curvature, which are processes that are essential to cellular physiology. Specifically, the prevailing structure-function paradigm posits that protein function only arises from specific structural features. However, our recent work has revealed that proteins lacking secondary structure – Intrinsically Disordered Proteins (IDPs) – can be potent sensors and generators of membrane curvature. The mechanisms for this functional behavior arises from the polyampholytic nature of these unfolded, amino acid chains. Interestingly, IDPs comprise ~40% of the human proteome but only a handful of IDPs have been examined in the context of protein-lipid interactions. Therefore, this paradoxical finding represents a significant, yet unexplored frontier in the field of membrane remodeling. Our most recent findings highlight an example of this disordered functionality in α-Synuclein, which is a neuronal protein heavily implicated with the onset of Parkinson’s Disease. In addition to the investigation of IDPs at biological membranes, this talk will briefly discuss some of our other research areas which include engineering strategies for mitigating lipid peroxidation in cellular membranes and the development of biomembrane-inspired technologies.