Title

Multivalent binding and selectivity in cell targeting, molecular recognition and receptor activation

Conference Dates

July 31-August 4, 2017

Abstract

MULTIVALENT BINDING AND SELECTIVITY IN CELL TARGETING, MOLECULAR RECOGNITION AND RECEPTOR ACTIVATION

Jure Dobnikar, Institute of Physics, Chinese Academy of Sciences, Beijing, Chin ; Department of Chemistry, University of Cambridge, UK ; School of physical sciences, University of Chinese Academy of Sciences

One of the key challenges in nano-science is to design nanoparticles that can recognize and target specific objects. One such example are ligand-coated nanoparticles binding to surfaces covered with receptors forming bonds with the ligands. The requirement of many applications is that the particles bind selectively to surfaces with receptors either above a threshold concentration or in a specific geometric arrangement. Such nanoparticles would enable precise functioning of nano machines, as well as selective targeting of cells in drug delivery. Similarly, many biological processes rely on chemical activation based on (macro-) molecular recognition. Also in this case, the receptors need to selectively bind to specific molecules to get activated. In recent years, it has been shown that "super-selectivity" can only be achieved with multiple weak reversible bonds where many ligands simultaneously bind to the surface receptors. Only in such systems, the fraction of bound particles varies sharply with the receptor concentration and nano-particles can be designed such that they approach the on-off binding behaviour required for super- selective targeting. I will report on our recent work on physics of multivalent binding and specifically address targeting cancer cells, molecular recognition and multivalent receptor activation by DNA-peptide complexes in the immune system.

Publications:

[1] N.W. Schmidt, F. Jin, R. Lande, T. Curk, W. Xian, L. Frasca, D. Frenkel, J. Dobnikar, M. Gilliet, G.C.L. Wong, Antimicrobial-peptide-DNA complexes amplify TLR9 activation via liquid-crystalline ordering, Nature Materials 14, 696 (2015)

[2] T. Curk, J. Dobnikar, D. Frenkel, Rational design of molecularly imprinted polymers, Soft Matter 12, 35 (2016)

[3] T. Curk, J. Dobnikar, and D. Frenkel, Optimal multivalent targeting of mem- branes with many distinct receptors, to appear in PNAS (2017)

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