Author interview: Dr. Subhankar Kundu was born in Gangarampur, West Bengal, India. He completed his BSc and MSc from Scottish Church College (University of Calcutta, 2014) and National Institute of Technology Rourkela (2016), respectively. He was the gold medallist during his MSc. Later he joined the Indian Institute of Science Education and Research Bhopal for PhD under the supervision of Prof. Abhijit Patra and completed his PhD in September 2022. His PhD thesis was based on the function-led design and deciphering the molecular self-assembly of π-conjugated fluorophores. Currently, Subhankar is working on molecular cell mechanics employing cellular force nanoscopy at University of Cincinnati, College of Medicine, Hoxworth Blood Center, USA as part of his post-doctoral research.
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Lab: Dr. Xuefeng Wang, University: Research Division, Hoxworth Blood Center College of Medicine, University of Cincinnati, OH, USA
The present study has unraveled a novel cellular adhesion structure, phagocytic adhesion rings (PARs), and a unique mechanism of phagocytosis employed by macrophages to dislodge particles from surfaces. These findings significantly advance our understanding of the intricate processes underlying macrophage-mediated clearance of surface-bound particles and have implications for various biological and biomedical contexts, including therapeutic interventions targeting phagocytic pathways.
What was the core problem you aimed to solve with this research?
Phagocytosis of surface-bound particles remains less explored compared to that of the phagocytosis of suspended particles. In Metazoan animals, surface-bound pathogens and debris are prevalent, necessitating efficient clearance mechanisms. Macrophages, strategically located throughout tissues, serve as the frontline defense by internalizing these particles through phagocytosis. However, the exact mechanisms by which macrophages overcome the attachment of surface-bound particles to tissue surfaces are not fully elucidated, and previous studies on this topic are limited. Thus, a comprehensive understanding of the general mechanism specialized for phagocytosis of surface-bound particles needs a careful relook.
“We discovered a novel phagocytosis mechanism specifically adapted to detach pathogens or particles adhering to tissues.” — Dr. Xuefeng Wang
How did you go about solving this problem?
To achieve the goal, we employed a comprehensive array of experimental tools and techniques including (i) cellular force sensors and force modulators to probe the forces exerted by macrophages during the process of particle internalization, (ii) surface functionalization to control particle attachment strength to substrates, enabling the investigation of phagocytic mechanisms under varying adhesion conditions, and (iii) immunostaining combined with advanced imaging modalities for the visualization of molecular interactions and dynamics at the cell-substrate interface, shedding light on the mechanisms underlying phagocytosis of adherent particles.

How would you explain your research outcomes (Key findings) to the non-scientific community?
We unveiled a novel mechanism of phagocytosis of surface-bound particles by macrophages (Fig. 1A). We showed that instead of directly binding to the particles, macrophages assemble unique cellular structures termed phagocytic adhesion rings (PARs) on the substrate, specifically encircling these particles. These PARs contain integrins and exhibit similar protein compositions to other integrin-mediated adhesion structures, such as focal adhesions (FAs; Fig. 1B). By imaging the integrin-transmitted forces within PARs at the cell-substrate interface, we have provided valuable insights into the biomechanical aspects of phagocytosis. The calibration of single integrin forces within the range of 12-54 pN suggests that these forces are crucial for providing the anchorage necessary to support ring-shaped actin structures on PARs (Fig. 1C). Furthermore, the systematic studies implied that these actin structures facilitate the lifting off surface-bound particles (Fig. 1D and Fig. 1E).
What are the potential implications of your findings for the field and society?
The findings from this study provide critical insights into how immune cells apply mechanical forces during phagocytosis, advancing our understanding of immune mechanobiology. By directly visualizing and quantifying these forces, this research enhances our knowledge of macrophage function in pathogen clearance, immune regulation, and inflammatory responses. These insights have broad implications for biomedical applications, including improving immunotherapies, optimizing drug delivery systems, and designing biomaterials that interact effectively with the immune system. Furthermore, understanding force-mediated immune responses could aid in developing treatments for diseases where macrophage activity is dysregulated, such as infections, cancer, and autoimmune disorders. This research bridges biophysics and immunology, contributing to both fundamental science and translational medicine.
What was the exciting moment during your research?
One of the most exciting moments during this study was the first successful visualization of macrophages actively exerting mechanical forces on particles in real-time. Capturing these dynamic interactions at the molecular level provided direct evidence of how force contributes to phagocytosis, transforming a theoretical concept into a tangible image. Another thrilling milestone was optimizing the imaging technique to resolve nanoscale forces with high sensitivity, revealing unexpected variations in force application depending on particle size, stiffness, and surface chemistry. Seeing these forces in action for the first time not only validated our approach but also opened new questions about how mechanical cues influence immune responses. Additionally, unexpected findings led to exciting discussions and new hypotheses, fueling further experiments and potential biomedical applications.
Reference Kundu, S., Pal, K., Pyne, A. et al. Force-bearing phagocytic adhesion rings mediate the phagocytosis of surface-bound particles. Nat Commun 16, 984 (2025). https://doi.org/10.1038/s41467-025-56404-w
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