Title: Microparticle traction force microscopy reveals subcellular force exertion patterns in immune cell–target interactions

Journal Article · · Nature Communications
 [1];  [2]; ORCiD logo [3];  [4];  [5];  [3]; ORCiD logo [6]; ORCiD logo [5]
  1. Stanford Univ., CA (United States). Dept. of Biochemistry; Univ. of Washington, Seattle, WA (United States). Dept. of Biology and Howard Hughes Medical Institute; DOE/OSTI
  2. Stanford Univ., CA (United States). Dept. of Mechanical Engineering
  3. Memorial Sloan Kettering Cancer Center, New York, NY (United States). Immunology Program
  4. Sloan Kettering Institute, New York, NY (United States). Developmental Biology Program
  5. Stanford Univ., CA (United States). Dept. of Biochemistry; Univ. of Washington, Seattle, WA (United States). Dept. of Biology and Howard Hughes Medical Institute
  6. Stanford Univ., CA (United States). Dept. of Mechanical Engineering

Force exertion is an integral part of cellular behavior. Traction force microscopy (TFM) has been instrumental for studying such forces, providing spatial force measurements at subcellular resolution. However, the applications of classical TFM are restricted by the typical planar geometry. Here, we develop a particle-based force sensing strategy for studying cellular interactions. We establish a straightforward batch approach for synthesizing uniform, deformable and tuneable hydrogel particles, which can also be easily derivatized. The 3D shape of such particles can be resolved with superresolution (<50 nm) accuracy using conventional confocal microscopy. We introduce a reference-free computational method allowing inference of traction forces with high sensitivity directly from the particle shape. We illustrate the potential of this approach by revealing subcellular force patterns throughout phagocytic engulfment and force dynamics in the cytotoxic T-cell immunological synapse. This strategy can readily be adapted for studying cellular forces in a wide range of applications.

Research Organization:
Stanford Univ., CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC)
Grant/Contract Number:
SC0010412
OSTI ID:
1624229
Journal Information:
Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 11; ISSN 2041-1723
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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