Dynamics and mechanics of wound healing

• Applicants: Dr. Alexey Chizhik; Professor Dr. Andreas Janshoff
• Subject Area: Statistical Physics, Nonlinear Dynamics, Complex Systems, Soft and Fluid Matter, Biological Physics
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 431012826

• Final Report Year: 2024

Final Report Abstract

Collective cell migration emerges from complex long-range cell-cell communication, influenced by factors such as force transmission, individual cell viscoelasticity, substrate interactions, and mechanotransduction. Our studies examine how changes in cell-substrate distance fluctuations, adhesion, and traction forces affect the collective migration in confluent monolayers and during gap closure. Epithelial monolayers are formed by either wild-type (WT) MDCKII cells or highly contractile zonula occludens (ZO)-1/2-depleted MDCKII cells (double knockdown [dKD]) – serving as a model phenotype. Our findings show that confluent dKD monolayers are formed by contractile cells that move more slowly and are less correlated than WT cells. This slower movement is associated with an increased substrate adhesion, reduced traction forces, a more compact shape, weaker cell-cell interactions, and fewer fluctuations in cell-substrate distance. The same is found for the gap-closure dynamics of these two cell lines. dKD cells generate more leader cells and do not assemble an actomyosin cable to close the gap quickly. Additionally, the depletion of basal actin and myosin highlights the significant role of short-range cell-substrate interactions, particularly those driven by basal actomyosin, in influencing the migration speed of the monolayer on a larger scale. MIET microscopy was successfully used to measure the spatial cell-substrate distance of the two cell lines confirming that dKD cells are closer to the substrate than WT cells. In this context, we also investigated the potential of different types of nanoparticles for MIET imaging. Unlike standard dye molecules, nanoparticles, including graphene dots and semiconductor nanocrystals, exhibit superior photostability and extended excited state lifetimes. These characteristics can potentially improve the resolution and image acquisition rate of MIET imaging. We conducted proof-of-principle measurements to demonstrate a concept for a super-resolution imaging method that relies on the excitation field density-dependent lifetime modulation of semiconductor nanocrystals.

Publications

• Radiative Rate Modulation Reveals Near‐Unity Quantum Yield of Graphene Quantum Dots. Advanced Optical Materials, 9(19).
  Ghosh, Subhabrata; Oleksiievets, Nazar; Enderlein, Jörg & Chizhik, Alexey I.
  
• Tight junction ZO proteins maintain tissue fluidity, ensuring efficient collective cell migration. openRxiv.
  Skamrahl, Mark; Pang, Hongtao; Ferle, Maximilian; Gottwald, Jannis; Rübeling, Angela; Maraspini, Riccardo; Honigmann, Alf; Oswald, Tabea A. & Janshoff, Andreas
  
• Excited state lifetime modulation in semiconductor nanocrystals for super-resolution imaging. Nanotechnology, 33(36), 365201.
  Ghosh, Subhabrata; Hollingsworth, Jennifer A.; Gallea, Jose Ignacio; Majumder, Somak; Enderlein, Jörg & Chizhik, Alexey I.
  
• Cellular segregation in cocultures is driven by differential adhesion and contractility on distinct timescales. Proceedings of the National Academy of Sciences, 120(15).
  Skamrahl, Mark; Schünemann, Justus; Mukenhirn, Markus; Pang, Hongtao; Gottwald, Jannis; Jipp, Marcel; Ferle, Maximilian; Rübeling, Angela; Oswald, Tabea A.; Honigmann, Alf & Janshoff, Andreas
  
• Excitation Intensity-Dependent Quantum Yield of Semiconductor Nanocrystals. The Journal of Physical Chemistry Letters, 14(10), 2702-2707.
  Ghosh, Subhabrata; Ross, Ulrich; Chizhik, Anna M.; Kuo, Yung; Jeong, Byeong Guk; Bae, Wan Ki; Park, Kyoungwon; Li, Jack; Oron, Dan; Weiss, Shimon; Enderlein, Jörg & Chizhik, Alexey I.
  
• HAV‐Peptides Attached to Colloidal Probes Faithfully Detect E‐Cadherins Displayed on Living Cells. Chemistry – A European Journal, 29(39).
  Toy, Silan; Dietz, Jörn; Naumann, Peter; Trothe, Janina; Thomas, Franziska; Diederichsen, Ulf; Steinem, Claudia & Janshoff, Andreas
  
• Cell-substrate distance fluctuations of confluent cells enable fast and coherent collective migration. Cell Reports, 43(8), 114553.
  Jipp, Marcel; Wagner, Bente D.; Egbringhoff, Lisa; Teichmann, Andreas; Rübeling, Angela; Nieschwitz, Paul; Honigmann, Alf; Chizhik, Alexey; Oswald, Tabea A. & Janshoff, Andreas