Chem. Engg. Seminar Series : Subhankar Kundu

Quantitative Molecular Tools for Measuring and Controlling Forces at Cell-Material Interfaces.

Mechanical forces transmitted across cell-material interfaces regulate adhesion, signaling, and cellular function, yet quantitatively resolving these forces at molecular length scales remains challenging.1 In this talk, I will present an interdisciplinary framework combining molecular engineering, DNA nanotechnology, fluorescence imaging, surface chemistry, and quantitative mechanobiology to measure and manipulate receptor-transmitted forces at biological interfaces.

A central focus will be the engineering of DNA-based molecular tension probes, in which mechanically responsive DNA constructs convert receptor-generated forces into measurable fluorescence signals. These probes provide a molecular-scale transduction mechanism linking an applied cellular force to an optical output and enable spatially resolved mapping of receptor forces. Using a double-stranded DNA-based integrative tension sensor (ITS), we quantified force transmission through platelet integrin αIIbβ3 and identified two spatially distinct force-generating regimes: a central, MLCK-regulated actomyosin system and a peripheral Rac1/Arp2/3-dependent actin-polymerization system. We further examined the relationship between substrate stiffness, molecular force transmission, and cellular response, providing a quantitative framework for understanding how cells mechanically interrogate material properties.

The same force-measurement strategy was extended to macrophage-particle interfaces, where quantitative force mapping revealed β2-integrin-mediated phagocytic adhesion rings surrounding surface-bound particles. These structures mechanically couple receptor adhesion with actin polymerization, generating forces that enable macrophages to overcome particle-surface adhesion and achieve particle detachment and internalization. This system illustrates how the balance between cell-generated forces and interfacial adhesion can determine the outcome of a biological transport process .

Finally, I will demonstrate how molecular structure-property relationships can be exploited to actively control cellular mechanics. By systematically tuning the excited-state properties and singlet-oxygen generation efficiencies of BODIPY photosensitizers, we established a quantitative connection between molecular structure, photophysical response, reactive oxygen species generation, integrin-force transmission, and platelet function. Increased photochemical efficiency produced correspondingly faster suppression of cellular force generation, spreading, adhesion, and aggregation. Together, these studies demonstrate how molecular-scale sensors and actuators can be engineered to quantify input-output relationships across biological interfaces, connecting molecular structure and material properties to force transmission and cellular response. This quantitative approach provides a foundation for designing force-responsive biomaterials, molecular sensors, and engineered cell-material interfaces for applications spanning mechanobiology, biomaterials, and biomedical engineering.

Bio:

Dr. Subhankar Kundu is a Postdoctoral Fellow in the Department of Biology at Indiana University Bloomington, USA, where he works at the interface of molecular engineering, biomaterials, and cellular mechanobiology. Prior to joining Indiana University, he conducted postdoctoral research with Prof. Xuefeng Wang at the University of Cincinnati and Iowa State University, developing DNA-based molecular tension sensors and quantitative fluorescence approaches to investigate how cells generate, transmit, and respond to mechanical forces. Dr. Kundu received his Ph.D. in Chemistry from IISER Bhopal, where his research centered on the molecular design, self-assembly, and photophysical properties of functional π-conjugated fluorescent materials. Building on this foundation in molecular and materials chemistry, his postdoctoral research has expanded toward the quantitative measurement and manipulation of forces at cell-material interfaces. His work has revealed distinct mechanisms of integrin-mediated force generation during platelet adhesion and identified force-bearing adhesion structures involved in macrophage phagocytosis. More recently, he has integrated molecular photophysics with mechanobiology, establishing connections between photosensitizer structure, reactive oxygen species generation, molecular force transmission, and cellular mechanical responses. His broader research vision is to develop molecular sensors, force-responsive materials, and quantitative imaging strategies that connect molecular-scale physicochemical processes with cellular behavior. His research has been published in journals including Nature Communications, Nano Letters, Chemistry of Materials, and Biophysical Journal.             

Google Scholar: https://scholar.google.com/citations?user=EcgPBW4AAAAJ&hl=en