报告主题：Tuning the binding selectivity in molecular recognition, targeting and activation
主 讲 人：Jure Dobnikar 教授（卢布尔雅那大学）
主 持 人：高永祥
时 间：2026年7月2日（四）16：00
地 点：致知楼706
嘉宾简介：
Jure Dobnikar graduated in theoretical physics from University of Ljubljana in 2001. He worked as a postdoctoral fellow at University of Konstanz and University of Graz, and later as a senior researcher at Jožef Stefan Institute in Ljubljana and at University of Cambridge. In 2014, he moved to Beijing, where he initially managed the International Soft Matter Research Center and was later appointed as a professor at the Institute of Physics, Chinese Academy of Sciences. He established the CECAM-BJ node with a mission to bring high quality scientific event organization and international exchange possibilities to China He is currently the node director. In 2026, he started his current position at the University of Ljubljana, where he is building a research group exploring soft and biological matter, colloidal interactions, self-assembly, non-equilibrium phenomena, active matter, bacterial motility, and multivalent binding in cellular targeting and activation processes.
报告摘要：
A prerequisite for functioning of vital biological processes is the ability to recognize specific conditions or situations and respond when (and only when) it is needed. This is particularly obvious in the processes involved in the immune response where failure to respond to an attack can be life-threatening, but so can a wrong response (autoimmune disorder). On a molecular level this means that living systems must be able to respond to the presence of specific molecules in an on-off manner, e.g., triggering a sharp response when external ligands are presented above a certain threshold density, but no response when they are not. As demonstrated by Martinez-Veracoechea and Frenkel studying binding of ligand-decorated probes to receptor-decorated surfaces [1], probes with ligands that form very strong bonds cannot be selective, while those with multiple ligands each forming a weak 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 multivalent binding for targeting cells with arbitrary receptor composition [2], which we further applied to design a new method for detecting microbial genome [3]. Moreover, we showed that the multivalent binding theory also underlies the activation of immune system response and can regulate the onset of autoimmune disorders [4]. In our recent study [5], we explored how tuning the inter–receptor attraction can enhance or suppress cellular response to external agents. In the presence of multivalent ligand–coated particles, the cells that operate close to critical conditions can switch receptor-clustering on or off in an almost stepwise fashion by small changes (less than kBT) of the inter–receptor attraction. This in turn provides a precise control over binding of multivalent external agents to their membranes. Based on our results, it is tempting to speculate that the immune system may tune the receptor attraction to activate or de-activate immune cells, if external ligands are presented above or below a certain threshold density. Our results highlight that universal physical mechanisms combining macromolecular assembly and statistical mechanics of multivalent binding can transform the non-specific (usually electrostatic) interactions into specific interactions that can efficiently control the processes in biomolecular systems.
[1] F. J. Martinez-Veracoechea, D. Frenkel, PNAS 108 10963 (2011)
[2] T. Curk, J. Dobnikar, D. Frenkel, PNAS 114 7210 (2017);
[3] T. Curk et al., PNAS 117 (16) 8719 (2020)
[4] N.W. Schmidt et al., Nature Materials 14 696 (2015)
[5] Z. Xie et al., PNAS 122 (7) e2417159122 (2025)
