Postdoctoral Researcher, University of California, San Diego


Development of bottom-up approaches for the construction of functional artificial cell membranes

The fabrication of artificial cells from purely synthetic components provides a novel methodology to reconstruct life’s functions within unnatural materials. Artificial cells have the potential to shed light on biological processes such as gene expression and energy transduction, as well as organize chemical reactions in nanoscale compartments. Remarkably, they also offer a unique opportunity to study how life emerged on Earth and possibly elsewhere. Therefore, there has been an increasing interest to develop novel strategies for the incorporation and/or integration of biological components in synthetic capsules to facilitate signaling responses, drug delivery, encapsulation and extended expression of biomolecules. An ambitious strategy is the bottom-up approach, which aims to systematically control the assembly of highly ordered membrane architectures with defined functionality. Bottom-up methodologies that assemble artificial cells from synthetic membranes are well suited for a range of applications, such as integrating functionalized vesicles with biological machinery and creating hybrid minimal cells using nonbiological chassis. My research is focused on the use of biomimetic bottom-up approaches to spontaneously generate and remodel phospholipid membranes from water-soluble starting materials. The orthogonality, high reaction rate, and biocompatibility of these methodologies are key features that make them a powerful option for the efficient encapsulation of relevant biomolecules. Additionally, my research explores the suitability of such bioorthogonal coupling reactions for driving the in situ formation of phospholipid membranes and concomitant spontaneous reconstitution of a variety of membrane proteins, with retention of functionality. These studies give us a deeper understanding of the nature of living systems that could bring new insights into the origin of cellular life, and provide novel synthetic chassis for advancing synthetic biology


Nonenzymatic biomimetic remodeling of phospholipids in synthetic liposomes

Abstract: Cell membranes have a vast repertoire of phospholipid species whose structures can be dynamically modified by enzymatic remodeling of acyl chains and polar head groups. Lipid remodeling plays important roles in membrane biology and dysregulation can lead to disease. Although there have been tremendous advances in creating artificial membranes to model the properties of native membranes, a major obstacle has been developing straightforward methods to mimic lipid membrane remodeling. Stable liposomes are typically kinetically trapped and are not prone to exchanging diacylphospholipids. Here, we show that reversible chemoselective reactions can be harnessed to achieve nonenzymatic spontaneous remodeling of phospholipids in synthetic membranes. Our approach relies on transthioesterification/acyl shift reactions that occur spontaneously and reversibly between tertiary amides and thioesters. We demonstrate exchange and remodeling of both lipid acyl chains and head groups. Using our synthetic model system we demonstrate the ability of spontaneous phospholipid remodeling to trigger changes in vesicle spatial organization, composition, and morphology as well as recruit proteins that can affect vesicle curvature. Membranes capable of chemically exchanging lipid fragments could be used to help further understand the specific roles of lipid structure remodeling in biological membranes.

Pub.: 20 Jul '16, Pinned: 29 Jun '17