Unless otherwise noted, all Seminar Series events are held at 3 p.m. in the MoSE "M" Building (Room G011). Refreshments are served outside of the room starting at 2:30 p.m.
Dr. Danielle J. Mai, Department of Chemical Engineering, Massachusetts Institute of Technology
“Engineering Hierarchical Polymers to Control Biomolecular Transport”
New materials that control specific biomolecular transport will be central to numerous technologies including biosensors, bioseparations, and tissue engineering. Natural systems such as nuclear pores routinely regulate molecular transport with remarkable specificity (>99.9% of proteins rejected) and speed (1,000 proteins per second per pore), but the biophysical mechanisms underlying selective nuclear transport remain unclear. The central channel of Dathe nuclear pore is filled with a disordered matrix of nucleoporin proteins, which inspires the development of a selective transport model based on protein binding, diffusion, and solubility in a polymer network.
In this seminar, I will present a continuum-scale transport model used to investigate the selective transport phenomena exhibited by nucleoporins. The transport model accounts for binding and diffusion of biomolecules in a polymer network. Specifically, target biomolecules exhibit diffusive behavior in bound and unbound molecular states, in comparison to inert biomolecules that exist only in an unbound state. Calculation of the flux ratio of target and inert molecules across a broad parameter space reveals key requirements for selective transport to occur in polymer networks. The model predicts two key principles for selective biomolecular transport by a polymer network: (1) entropic repulsion of non-interacting molecules and (2) affinity-mediated permeation of interacting molecules through a walking mechanism. These principles guide the design and synthesis of artificial, nucleopore-inspired polymer gels that replicate the selective transport function of nuclear pore proteins. Biophysical characterization reveals the importance of entropic size exclusion, moderate binding affinity, and bound-state diffusion processes in selective hydrogel permeability and transport, in agreement with predictions of the selective transport model. Overall, this work presents a new paradigm for selective transport that critically enables the design of polymer hydrogels to control the transport of multi-receptor biomolecules including therapeutic proteins, immunoglobulins, and broad classes of biotoxins.
Danielle J. Mai is an Arnold O. Beckman Postdoctoral Fellow in the Department of Chemical Engineering at MIT. She earned her B.S.E. in Chemical Engineering from the University of Michigan and her M.S. and Ph.D. in Chemical Engineering from the University of Illinois at Urbana-Champaign under the guidance of Prof. Charles M. Schroeder. Danielle’s research integrates precise biopolymer engineering with multiscale experimental characterization to advance biomaterials development and to enhance fundamental understanding of soft matter physics. In Professor Bradley D. Olsen's group at MIT, Danielle is currently engineering materials with selective biomolecular transport properties, elucidating mechanisms of toughness and extensibility in entangled associative hydrogels, and developing high-throughput methods for the discovery of polypeptide materials.