(6ap) Engineering Biomimetic Membranes

Cells coordinate a variety of physical and chemical processes to yield complex and dynamic behaviors. My research examines the most basic physical and chemical processes that underlie cellular behaviors. I build synthetic models of cellular membranes from phospholipids, fatty acids, or diblock-copolymers and use molecular biology and synthetic chemistry techniques to generate chemically activated nucleotides and RNA polynucleotides. With these building blocks, I construct bilayer membranes containing RNA and study how biophysical events, like membrane deformation, growth, and division can be replicated and even triggered in synthetic systems, and study how genetic processes like non-enzymatic RNA replication can be conducted without the aide of complicated cellular machinery.  By studying and recreating how simple biophysical and genetic processes can be conducted with a minimal number of known components, I aim to advance our understanding of the basic thermodynamic processes that guide higher-order cellular behavior as well as create a tool kit of cellular behaviors that we can assemble to create intelligent devices for future applications in medicine and biotechnology. My research, therefore, focuses on two complementary experimental approaches 1) Designing responsive synthetic membranes and 2) Studying how RNA processes can be coupled to synthetic membranes. 

The bilayer membrane, typically formed from phospholipids, provides a powerful platform to assemble biological and synthetic molecules alike. Beyond phospholipids, diblock-copolymers have emerged as a powerful class of amphiphiles to generate membranes with a wide variety of physical and chemical properties. As a doctoral student with Professor Daniel Hammer, I have studied to how to design diblock-copolymer membranes. Specifically, I designed membranes responsive to both light and mechanical stimuli. In addition to vesicle-membrane design, I have used soft lithography and microfluidic techniques to create micro-patterned surfaces and controlled vesicle architectures. These techniques enable the construction of larger scale, organized patterns of vesicles to better study vesicle-vesicle and vesicle-cell behaviors in spatially and chemically controlled environments.

As a postdoctoral researcher with Professor Jack Szostak, I have studied how short RNA polynucleotides can be complexed with fatty acid and phospholipid membranes. Using synthetic peptides, I have shown that RNA can be localized to the surface of both fatty acid and phospholipid membranes via electrostatic interactions with short peptides. Our work with synthetic membranes enables a platform to study how membrane composition and peptide sequence influence RNA-membrane binding and opens the door for studying how membranes can enhance reactions with surface-localized polynucleotides. I have also engineered vesicle systems that display temperature and divalent cation-gated RNA permeability, enabling the transport of short RNA polynucleotides into vesicle membranes to participate in non-enzymatic RNA replication chemistry. The construction of a responsive membrane that enables polynucleotide passage could advance the design of vesicle bioreactors or sensors that utilize short oligonucleotides as substrates.

Bringing together emerging engineering methods in material science and synthetic biology, I aim to construct macromolecular assemblies that can coordinate both membrane biophysical processes and genetic transcription and translation events to yield particles capable of complex signaling and responsive behaviors.