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Polymer Gels Adapted From and Inspired by the Nuclear Pore

Speaker: Bradley D. Olsen, Massachusetts Institute of Technology
Series: Saville Lectures
Location: Maeder Hall Auditorium, Andlinger Center for Energy and the Environment
Date/Time: Wednesday, March 28, 2018, 4:00 p.m. - 5:00 p.m.

Nucleoporins are a category of protein that forms pores within the nuclear envelope, regulating transport of biomolecules into and out of the nucleus.  The gels formed by these proteins within the nuclear pores demonstrate the remarkable ability to selectively restrict transport to just a small subset of nuclear transport proteins and their cargo while enabling high flux across the membrane.  This combination of high permeability and selectivity makes them attractive as both a fundamental biological system and a model for the development of new synthetic materials.  Herein, we show that using a consensus repeat analysis we can extract a minimal repeat sequence from one of the most widely studied nucleoporins, Nsp1.  When this repeat sequence is polymerized, it forms a nucleoporin-like protein (NLP) that can mimic the properties of the natural protein with a dramatically simplified amino acid sequence.  This sequence provides the ability to selectively transport proteins and to selectively enrich and transport proteins down to the 1-10 nM level.  It also provides a model for exploring the effect of mutations on nucleoporin gel function:  using a combination of mutation studies to the base NLP sequence and biophysical characterization, we can gain insight into the design of the NLP repeat sequence and the factors affecting transport rate and selectivity.
Inspired by these results from protein engineering, we aspired to better understand the mechanism of function in these systems through modelling and to recapitulate that function in a fully synthetic material system.  Using concepts of associative polymer diffusion, we put forward a hypothesis to explain the function of these simplified NLPs based on the presence of walking and hopping diffusive modes in the gels.  This hypothesis suggests design rules which allow the same transport properties observed in NLPs to be replicated in peptide-functionalized poly(ethylene glycol) (PEG) gels, completing the design cycle of adapting the performance of a natural material to a fully synthetic system based on insight into its fundamental transport mechanism.  This shows great potential for advances in protein separation technology.