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  2. Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells

Chiral Cell Nanomechanics Originated in Clockwise/Counterclockwise Biofunctional Microarrays to Govern the Nuclear Mechanotransduction of Mesenchymal Stem Cells

  • ACS Appl Mater Interfaces. 2023 Oct 9. doi: 10.1021/acsami.3c11188.
Yongtao Wang 1 Xiaolan Tong 1 Xiaohui Shi 1 Tarun Keswani 2 Emeli Chatterjee 3 Lei Chen 4 5 Guoping Li 2 Kyubae Lee 6 Tao Guo 7 Yan Yu 4 5
Affiliations

Affiliations

  • 1 Shanghai Engineering Research Center of Organ Repair, School of Medicine, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China.
  • 2 Center for Immunological and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, United States.
  • 3 Cardiovascular Division of the Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States.
  • 4 Department of Spine Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • 5 Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration, Ministry of Education, Department of Spine Surgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai 200065, China.
  • 6 Department of Medical Engineering, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
  • 7 Department of Orthopaedics, Guizhou Provincial People's Hospital, Guiyang 550002, China.
Abstract

Cell chirality is extremely important for the evolution of cell morphogenesis to manipulate cell performance due to left-right asymmetry. Although chiral micro- and nanoscale biomaterials have been developed to regulate cell functions, how cell chirality affects cell nanomechanics to command nuclear mechanotransduction was ambiguous. In this study, chiral engineered microcircle arrays were prepared by photosensitive cross-linking synthesis on Cell Culture plates to control the clockwise/counterclockwise geometric topology of stem cells. Asymmetric focal adhesion and Cytoskeleton structures could induce chiral cell nanomechanics measured by atomic force microscopy (AFM) nanoindentation in left-/right-handed stem cells. Cell nanomechanics could be enhanced when the construction of mature focal adhesion and the assembly of actin and Myosin cytoskeletons were well organized in chiral engineered stem cells. Curvature angles had a negative effect on cell nanomechanics, while cell chirality did not change cytoskeletal mechanics. The biased Cytoskeleton tension would engender different nuclear mechanotransductions by yes-associated protein (YAP) evaluation. The chiral stimuli were delivered into the nuclei to oversee nuclear behaviors. A strong cell modulus could activate high nuclear DNA synthesis activity by mechanotransduction. The results will bring the possibility of understanding the interplay of chiral cell nanomechanics and mechanotransduction in nanomedicines and biomaterials.

Keywords

DNA synthesis; FA and cytoskeleton; YAP mechanotransduction; chiral nanomechanics; engineered stem cells.

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