Speaker:Prof. Jure Dobnikar（Institute of Physics, Chinese Academy ofSciences）
Time:March 24, 2025 10:00 AM
Location:Lecture Room 313,AISMST
Abstract:
A prerequisite for functioningof vital biological processes is the ability to recognize specific conditionsor situations and respond when (and only when) it is needed. This isparticularly obvious in the processes involved in the immune response wherefailure to respond to an attack can be life-threatening, but so can a wrongresponse (autoimmune disorder). On a molecular level this means that livingsystems must be able to respond to the presence of specific molecules in anon-off manner, e.g., triggering a sharp response when external ligands arepresented above a certain threshold density, but no response when they are not.
As demonstrated byMartinez-Veracoechea and Frenkel studying binding of ligand-decorated probes toreceptor-decorated surfaces , probes with ligands that form very strongbonds cannot be selective, while those with multiple ligands each forming aweak bond can exploit the combinatorial entropy of binding to“super-selectively” distinguish between “target” and “non-target” surfaces.Here, I will present our theory of optimal multivalentbinding for targeting cells with arbitrary receptor composition , which wefurther applied to design a new method for detecting microbial genome . Moreover,we showed that the multivalent binding theory also underlies the activation ofimmune system response and can regulate the onset of autoimmune disorders .
In our recent study ,we explored how tuning the inter–receptor attraction can enhance or suppresscellular response to external agents. In the presence of multivalentligand–coated particles, the cells that operate close to critical conditions canswitch receptor-clustering on or off in an almost stepwise fashion by smallchanges (less than kBT)of the inter–receptor attraction. This in turn provides a precise control overbinding of multivalent external agents to their membranes. Based on ourresults, it is tempting to speculate that the immune system may tune thereceptor attraction to activate or de-activate immune cells, if externalligands are presented above or below a certain threshold density.
Our results highlightthat universal physical mechanisms combining macromolecular assembly andstatistical mechanics of multivalent binding can transform the nonspecific (usuallyelectrostatic) interactions into specific interactions that can efficientlycontrol the processes in biomolecular systems.
BriefBiography:
Jure Dobnikar graduated in theoretical physics fromUniversity of Ljubljana in 2001. He worked as a postdoctoral fellow at Universityof Konstanz and University of Graz, and later as a senior researcher at JožefStefan Institute in Ljubljana and at University of Cambridge. In 2014, he movedto Beijing to manage the International Soft Matter Research Center at BUCT andin 2016 he accepted a permanent position at the Institute of Physics, ChineseAcademy of sciences, where he is currently a full professor and the leader ofthe SM9 research group. His research interests are in physical modelling ofsoft and biological matter, particularly colloidal interactions, self-assembly,non-equilibrium phenomena, active matter, bacterial motility, and multivalentbinding in cellular targeting and activation processes. He is also the directorof the newly established CECAM-CN node with a mission to bring high qualityscientific event organization and international exchange possibilities toChina.