OpenLB
Open Library of Bioscience
Advanced Search
Proceedings of the National Academy of Sciences of the United States of America
Mar 25, 2025;122 (12): e2322762122.

Cell-matrix feedback controls stretch-induced cellular memory and fibroblast activation.

Yuan Hong, Xiangjun Peng, Haomin Yu, Mohammad Jafari, Delaram Shakiba, Yuxuan Huang, Chengqing Qu, Ermia E Melika, Andrew K Tawadros, Aliza Mujahid, Yin-Yuan Huang, Jacob A Sandler, Kenneth M Pryse, Justin M Sacks, Elliot L Elson, Guy M Genin, Farid Alisafaei
Author Information
  1. Yuan Hong: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130. ORCID
  2. Xiangjun Peng: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  3. Haomin Yu: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  4. Mohammad Jafari: NSF Science and Technology Center for Engineering Mechanobiology, Newark, NJ 07102. ORCID
  5. Delaram Shakiba: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  6. Yuxuan Huang: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  7. Chengqing Qu: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  8. Ermia E Melika: NSF Science and Technology Center for Engineering Mechanobiology, Newark, NJ 07102.
  9. Andrew K Tawadros: NSF Science and Technology Center for Engineering Mechanobiology, Newark, NJ 07102.
  10. Aliza Mujahid: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  11. Yin-Yuan Huang: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  12. Jacob A Sandler: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  13. Kenneth M Pryse: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  14. Justin M Sacks: Division of Plastic and Reconstructive Surgery, Washington University in St. Louis School of Medicine, St. Louis, MO 63110.
  15. Elliot L Elson: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130.
  16. Guy M Genin: NSF Science and Technology Center for Engineering Mechanobiology, Washington University in St. Louis, St. Louis, MO 63130. ORCID
  17. Farid Alisafaei: NSF Science and Technology Center for Engineering Mechanobiology, Newark, NJ 07102.
PMID: 40100625 DOI: 10.1073/pnas.2322762122

Abstract

Mechanical stretch can activate long-lived changes in fibroblasts, increasing their contractility and initiating phenotypic transformations. This activation, critical to wound healing and procedures such as skin grafting, increases with mechanical stimulus for cells cultured in two-dimensional but is highly variable in cells in three-dimensional (3D) tissue. Here, we show that static mechanical stretch of cells in 3D tissues can either increase or decrease fibroblast activation depending upon recursive cell-extracellular matrix (ECM) feedback and demonstrate control of this activation through integrated in vitro and mathematical models. ECM viscoelasticity, signaling dynamics, and cell mechanics combine to yield a predictable, but nonmonotonic, relationship between mechanical stretch and long-term cell activation. Results demonstrate that feedback between cells and ECM determine how cells retain memory of mechanical stretch and have direct implications for improving outcomes in skin grafting procedures.

Keywords

cell-matrix feedback fibroblasts mechanical memory mechanobiology mechanotransduction

References

  1. Sci Adv. 2021 Jan 8;7(2): [PMID: 33523987]
  2. J Biomech. 2008 Oct 20;41(14):2964-71 [PMID: 18805531]
  3. Nat Rev Mol Cell Biol. 2014 Dec;15(12):802-12 [PMID: 25355505]
  4. Adv Wound Care (New Rochelle). 2019 Feb 1;8(2):39-48 [PMID: 30809421]
  5. Acta Biomater. 2025 Jan 1;191:325-335 [PMID: 39581335]
  6. ACS Nano. 2020 Jul 28;14(7):7868-7879 [PMID: 32286054]
  7. Nucleus. 2018 Jan 1;9(1):9-19 [PMID: 29099288]
  8. Acta Biomater. 2022 Dec;154:290-301 [PMID: 36243372]
  9. BMC Syst Biol. 2017 May 16;11(1):55 [PMID: 28511648]
  10. Acta Biomater. 2016 Jun;37:28-37 [PMID: 27015891]
  11. J Burn Care Res. 2006 Nov-Dec;27(6):864-8 [PMID: 17091084]
  12. Ann Biomed Eng. 2012 Aug;40(8):1666-78 [PMID: 22427196]
  13. J Dtsch Dermatol Ges. 2020 Apr;18(4):341-364 [PMID: 32291926]
  14. Burns. 2008 Mar;34(2):153-63 [PMID: 18226455]
  15. Dermatol Ther. 2020 Nov;33(6):e14393 [PMID: 33037725]
  16. Nat Commun. 2015 Jan 22;6:5942 [PMID: 25608644]
  17. Integr Biol (Camb). 2012 Apr;4(4):410-21 [PMID: 22410748]
  18. Mol Biol Cell. 2018 Dec 1;29(25):3039-3051 [PMID: 30256731]
  19. Biophys J. 2008 Apr 1;94(7):2906-13 [PMID: 18178644]
  20. Int J Organ Transplant Med. 2021;12(1):44-51 [PMID: 34987732]
  21. Burns. 2013 Dec;39(8):1577-87 [PMID: 23880091]
  22. Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11349-54 [PMID: 23798429]
  23. Nature. 2020 Aug;584(7822):535-546 [PMID: 32848221]
  24. Biophys J. 2014 Aug 19;107(4):825-33 [PMID: 25140417]
  25. Adv Wound Care (New Rochelle). 2021 May;10(5):281-292 [PMID: 33733885]
  26. Clin Anat. 2014 Mar;27(2):162-8 [PMID: 24038134]
  27. Nat Commun. 2021 Oct 28;12(1):6229 [PMID: 34711824]
  28. Adv Sci (Weinh). 2018 Dec 10;6(3):1801483 [PMID: 30775233]
  29. Biophys J. 2000 Nov;79(5):2353-68 [PMID: 11053115]
  30. J Cell Sci. 1989 Jun;93 ( Pt 2):255-66 [PMID: 2482296]
  31. Nat Mater. 2014 Jun;13(6):645-52 [PMID: 24633344]
  32. Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):14043-14048 [PMID: 27872289]
  33. Interface Focus. 2016 Feb 6;6(1):20150067 [PMID: 26855753]
  34. Biochim Biophys Acta. 2013 Jul;1832(7):884-90 [PMID: 23434892]
  35. Sci Rep. 2015 Nov 23;5:16895 [PMID: 26592929]
  36. Phys Rev Lett. 1985 Oct 28;55(18):1896-1899 [PMID: 10031955]
  37. Burns. 2022 Feb;48(1):215-227 [PMID: 34716045]
  38. Integr Biol (Camb). 2009 Mar;1(3):252-9 [PMID: 20023736]
  39. J Am Acad Dermatol. 2016 Apr;74(4):607-25; quiz 625-6 [PMID: 26979353]
  40. Adv Ther. 2017 Mar;34(3):599-610 [PMID: 28108895]
  41. Proc Natl Acad Sci U S A. 2019 Jul 2;116(27):13200-13209 [PMID: 31209017]
  42. Nat Mater. 2017 Mar;16(3):379-389 [PMID: 27798620]
  43. Adv Wound Care (New Rochelle). 2015 Sep 1;4(9):560-582 [PMID: 26339534]
  44. Mol Biol Cell. 2023 May 15;34(6):ar54 [PMID: 36696158]
  45. Soft Matter. 2021 Jan 22;17(2):241-253 [PMID: 33136113]
  46. Ann Plast Surg. 2003 Feb;50(2):212-4 [PMID: 12567064]
  47. Clin Dermatol. 2010 Sep-Oct;28(5):519-26 [PMID: 20797512]
  48. J Mech Behav Biomed Mater. 2012 Jan;5(1):139-48 [PMID: 22100088]
  49. Clin Dermatol. 2005 Jul-Aug;23(4):332-7 [PMID: 16023927]
  50. J Biol Chem. 1993 Nov 15;268(32):23850-5 [PMID: 8226923]
  51. J Burn Care Res. 2006 Jul-Aug;27(4):508-14 [PMID: 16819356]
  52. Integr Biol (Camb). 2010 Sep;2(9):435-42 [PMID: 20725677]
  53. PLoS One. 2012;7(12):e45512 [PMID: 23300512]
  54. J Biomech Eng. 2003 Oct;125(5):719-25 [PMID: 14618931]
  55. Ann Biomed Eng. 2006 Sep;34(9):1475-82 [PMID: 16874557]
  56. Curr Opin Cell Biol. 2010 Oct;22(5):669-76 [PMID: 20850289]

Grants

  1. HFSP - RGP016/2024/Human Frontier Science Program (HFSP)
  2. R01 DK131177/NIDDK NIH HHS
  3. OIA-2219142/NSF (NSF)
  4. CMMI 1548571/NSF (NSF)
  5. R01 HL159094/NHLBI NIH HHS
  6. R01 AR077793/NIAMS NIH HHS
  7. DMR 2105150/NSF (NSF)

MeSH Term

Fibroblasts
Extracellular Matrix
Animals
Stress, Mechanical
Models, Biological
Humans
Mice
Feedback, Physiological
Journal Article
Article has an altmetric score of 12

Word Cloud

Created with Highcharts 10.0.0activationmechanicalcellsstretchfeedbackECMmemorycanfibroblastsproceduresskingrafting3DfibroblastdemonstratecellMechanicalactivatelong-livedchangesincreasingcontractilityinitiatingphenotypictransformationscriticalwoundhealingincreasesstimulusculturedtwo-dimensionalhighlyvariablethree-dimensionaltissueshowstatictissueseitherincreasedecreasedependinguponrecursivecell-extracellularmatrixcontrolintegratedvitromathematicalmodelsviscoelasticitysignalingdynamicsmechanicscombineyieldpredictablenonmonotonicrelationshiplong-termResultsdetermineretaindirectimplicationsimprovingoutcomesCell-matrixcontrolsstretch-inducedcellularcell-matrixmechanobiologymechanotransduction

Similar Articles

Cited By

No available data.