BEGIN:VCALENDAR VERSION:2.0 PRODID:-//Talks.cam//talks.cam.ac.uk// X-WR-CALNAME:Talks.cam BEGIN:VEVENT SUMMARY:Multivalent binding and selectivity in molecular targeting\, recog nition and activation - Jure Dobnikar (Chinese Academy of Sciences) DTSTART:20231122T130000Z DTEND:20231122T140000Z UID:TALK208705@talks.cam.ac.uk DESCRIPTION:A prerequisite for biological processes involving recognition\ , targeting and activation  \;is the ability to selectively bind to sp ecific cells or surfaces. An ideal &ldquo\;super-selective&rdquo\; probe e xploits multivalent binding between its ligands and target receptors to re cognize and exclusively bind to target surfaces. I will present our work o n physics of multivalent binding and its application to targeting cells\, detecting microbial genome\, and activation of immune system response. Spe cifically\, we derived design principles for optimal targeting of multicom ponent receptor-covered surfaces [1] and studied selective endocytosis of nanoparticles through cell membranes by engineering the composition of the membrane [2].  \;We also studied the efficiency of genome detection b y binding surface-grafted probes to the genomic DNA [3]. We demonstrate th at the sensitivity and selectivity of existing screening methods can be si gnificantly enhanced with multivalent targeting. Finally\, we explored act ivation processes triggering the immune system response with a combination of X-ray scattering\, computer simulations\, statistical mechanics and in -vitro measurements [4\,5]. Our results provide a mechanism of receptor ac tivation in certain autoimmune disorders and suggest suggest that the TLR9 -mediated immune response can be modulated deterministically offering new treatment possibilities. Furthermore\, our work highlights that simple phy sical mechanism combining self-assembly of macromolecular clusters and mul tivalent binding is governing the emergence of specificity from non-specif ic electrostatic interactions.\nReferences:\n[1] T. Curk\, J. Dobnikar\, D . Frenkel\, PNAS \;114 7210 (2017)\n[2] T. Curk\, et al.\, Nano Lett. 18 5350 (2018)\n[3] T. Curk et al.\, PNAS 117 (16) 8719 (2020)\n[4] N.W. S chmidt et al.\, Nature Materials 14 696 (2015) \n[5] E.Y. Lee et al.\, ACS Nano 11 (12) 12145 (2017) LOCATION:Seminar Room 2\, Newton Institute END:VEVENT END:VCALENDAR