Welcome to our lab! Our vision is to reverse engineer lipid membrane function as a route to understanding cellular physiology and constructing clinically translatable materials and systems. The health of cells and tissues relies on communication of biochemical instructions across membrane interfaces. Through quantitative molecular-scale measurements and the design of biomimetic materials, research in our laboratory aims to understand the physical basis of cellular membrane organization and develop novel therapeutic systems.
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Membrane Biophysics​
Our work in membrane biophysics aims to probe the mechanisms by which membranes are organized and shaped. Our lab was the first to demonstrate that protein crowding can provide a potent driving force for membrane bending (Stachowiak et al. NCB 2012) and fission (Snead et al. PNAS 2017). More recently we have shown that intrinsically disordered proteins, owing to their high conformational entropy, are key drivers (Busch et al. NComms 2015) and sensors (Zeno et al. N Comms 2018) of membrane curvature. Our ongoing work seeks to elucidate the role of protein networks in sensing and stabilizing membrane shape.
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Membrane Biology
Our work in membrane biology seeks to understand and control dynamic processes that occur at cellular membranes. We have recently demonstrated that the partitioning of receptors to clathrin coated structures can be explained by simple thermodynamic relationships (DeGroot et al. BiophysJ 2018). These relationships can be used to predict how receptors compete for space within crowded endocytic structures and how receptor-receptor binding interactions create collaborations that promote robust uptake (Zhao et al. BiophysJ 2019). Our ongoing work seeks to elucidate the mechanisms by which curved membrane structures are initiated in the cell.
Biophysics of Protein Condensates
Actin polymerization and bundling
Our research on protein condensates aims to elucidate their biophysical characteristics and functional roles in specific cellular events. Recently, we demonstrated that early endocytic proteins can form liquid-like condensates, where their liquid properties play an important role in catalyzing endocytosis (Day et al., Nat. Cell Biol. 2021). Furthermore, we revealed that the actin polymerase and bundling protein, VASP, forms liquid-like condensates that drive actin polymerization and filament bundling. . These condensates deform as the rigidity of polymerized actin filaments overcomes the surface tension of the condensate (Graham et al. Nat. Phys. 2023). Another noteworthy finding is the transmembrane coupling of liquid-like protein condensates, demonstrated using a suspended two-dimensional reconstituted membrane. This discovery could contribute to information transfer across the cell membrane (Lee et al., Nat. Commun. 2023).
Transmembrane condensate coupling
Biologically Inspired Therapeutic Delivery
Our work on membrane-derived therapeutics borrows concepts from biology and biophysics to overcome the barriers to drug delivery. Our lab was the first to demonstrate that using engineered membrane vesicles to harness the gap junction network can dramatically increase the efficiency of chemotherapeutic delivery (Gadok et al. JACS 2016). More recently we have shown that membrane phase separation can be used to promote membrane fusion, resulting in the release of macromolecular cargos into the cytoplasm (Imam et al. CMBE Young Innovator Award 2017). Our ongoing work is using molecular engineering approaches to develop gap junction-based vehicles for multiple therapeutics, the efficacy of which is being tested in vitro ( Trementozzi et al. ACS Biomaterals Sci & Eng, 2022) and in vivo (Trementozzi et al. ACS Biomaterials Sci & Eng, 2020). Additionally, our lab is working to identify the physical and biochemical properties that enable efficient uptake of therapeutic carriers by endocytosis. Our recent work has identified the fundamental coupling between particle size, rigidity, and targeting (Ashby et al, ACS Applied Materials and Interfaces, 2023).