Macromolecular separations are critical in a wide variety of technologies from industrial protein purification to biological toxin removal to blood diagnostics. In many cases, targets of interest are present at low concentrations and exhibit chemical and physical similarities to impurities. Biological membranes exhibit remarkable functionality as selective filters with the potential to critically advance macromolecular separation technologies. One such example is the nuclear envelope, which regulates the transport of biomolecules across the nuclear membrane to protect the genetic information of a cell. Nuclear pores facilitate the rapid passage of macromolecules (1,000 proteins per second) with immense selectivity (&lt; 0.1% of all proteins allowed). Although selective transport mechanisms in the nuclear pore complex remain unclear, nature inspires our development of polymeric materials for biomolecular separations.<br/><br/>Here, we demonstrate the possibility for a new filtration mechanism, where transport of a selective binding species through a membrane is accelerated due to the selective binding interaction. We present a continuum-scale transport model inspired by selective transport phenomena observed in nucleoporin-like protein gels. The transport model accounts for binding and diffusion of macromolecules in a polymer network. Specifically, target macromolecules exhibit diffusive behavior in bound and unbound molecular states, in comparison to inert macromolecules 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; namely, bound-state diffusion processes drive selective macromolecular transport through a membrane. Brownian dynamics simulations explore the impact of binding characteristics on diffusion, enabling the development of a physical theory describing the mechanisms of selective transport. Understanding from the selective transport theory guides the design and synthesis of artificial nucleopore-inspired polymers, which perform selective bioseparations in a proof-of-principle study. In ongoing work, we are characterizing selective transport behaviors in various natural and artificial systems. This research will critically enable the development a new paradigm for biomolecular separation technologies ranging from biotoxin removal to blood-based diagnostics to therapeutic monoclonal antibody purification.

New mechanism for selective macromolecular filtration in polymer networks

254th National Meeting (2017)

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