Chemo-Mechanical Factors That Limit Cellular Force Generation
Cellular traction forces that are dependent on actin-myosin activity are necessary for numerous developmental and physiological processes. As traction force emerges as a promising cancer biomarker there is a growing need to understand force generation in response to chemical and mechanical cues. Our...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-02-01
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| Series: | Frontiers in Physics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphy.2022.831776/full |
| _version_ | 1819282865179852800 |
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| author | Esteban Vazquez-Hidalgo Carly M. Farris Amy C. Rowat Parag Katira Parag Katira |
| author_facet | Esteban Vazquez-Hidalgo Carly M. Farris Amy C. Rowat Parag Katira Parag Katira |
| author_sort | Esteban Vazquez-Hidalgo |
| collection | DOAJ |
| description | Cellular traction forces that are dependent on actin-myosin activity are necessary for numerous developmental and physiological processes. As traction force emerges as a promising cancer biomarker there is a growing need to understand force generation in response to chemical and mechanical cues. Our goal is to present a unified modeling framework that integrates actin-myosin activity, substrate stiffness, integrin bond type, and adhesion complex dynamics to explain how force develops under specific conditions. Our simulation results show that substrate stiffness and number of myosin motors contribute to the maximum actin-myosin forces that can be generated but do not solely control the force transmitted by the cells to the surface, i.e., the traction force. The kinetics of the bonds between the cell and the substrate plays an equally important role. Overall, we find that while the cell can generate large actin-myosin forces in individual stress fibers (> 300 pN), the maximum force transmitted to the surface per cell-substrate attachment only reaches a fraction of these values (approx. 50 pN). Traction stress, the sum of forces transferred by all cell-substrate attachments in a unit area, is biphasic or sigmoidal with increasing substrate stiffness depending on the number of active myosin motors generating forces. Finally, we conclude that adhesions < 1 μm2 generate widely variable traction forces and that impulse, the magnitude and duration of a force generating event, is a key limiting factor in traction stress. |
| first_indexed | 2024-12-24T01:22:22Z |
| format | Article |
| id | doaj.art-00d6349ad22547b98a3ad2e567396875 |
| institution | Directory Open Access Journal |
| issn | 2296-424X |
| language | English |
| last_indexed | 2024-12-24T01:22:22Z |
| publishDate | 2022-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physics |
| spelling | doaj.art-00d6349ad22547b98a3ad2e5673968752022-12-21T17:22:36ZengFrontiers Media S.A.Frontiers in Physics2296-424X2022-02-011010.3389/fphy.2022.831776831776Chemo-Mechanical Factors That Limit Cellular Force GenerationEsteban Vazquez-Hidalgo0Carly M. Farris1Amy C. Rowat2Parag Katira3Parag Katira4Computational Science Research Center, San Diego State University, San Diego, CA, United StatesMechanical Engineering, San Diego State University, San Diego, CA, United StatesDepartment of Integrative Biology and Physiology, University of California Los Angeles, Los Angeles, CA, United StatesComputational Science Research Center, San Diego State University, San Diego, CA, United StatesMechanical Engineering, San Diego State University, San Diego, CA, United StatesCellular traction forces that are dependent on actin-myosin activity are necessary for numerous developmental and physiological processes. As traction force emerges as a promising cancer biomarker there is a growing need to understand force generation in response to chemical and mechanical cues. Our goal is to present a unified modeling framework that integrates actin-myosin activity, substrate stiffness, integrin bond type, and adhesion complex dynamics to explain how force develops under specific conditions. Our simulation results show that substrate stiffness and number of myosin motors contribute to the maximum actin-myosin forces that can be generated but do not solely control the force transmitted by the cells to the surface, i.e., the traction force. The kinetics of the bonds between the cell and the substrate plays an equally important role. Overall, we find that while the cell can generate large actin-myosin forces in individual stress fibers (> 300 pN), the maximum force transmitted to the surface per cell-substrate attachment only reaches a fraction of these values (approx. 50 pN). Traction stress, the sum of forces transferred by all cell-substrate attachments in a unit area, is biphasic or sigmoidal with increasing substrate stiffness depending on the number of active myosin motors generating forces. Finally, we conclude that adhesions < 1 μm2 generate widely variable traction forces and that impulse, the magnitude and duration of a force generating event, is a key limiting factor in traction stress.https://www.frontiersin.org/articles/10.3389/fphy.2022.831776/fullcell mechanobiologyfocal adhesionstraction forcesactin-myosin contractilitysubstrate stiffness |
| spellingShingle | Esteban Vazquez-Hidalgo Carly M. Farris Amy C. Rowat Parag Katira Parag Katira Chemo-Mechanical Factors That Limit Cellular Force Generation Frontiers in Physics cell mechanobiology focal adhesions traction forces actin-myosin contractility substrate stiffness |
| title | Chemo-Mechanical Factors That Limit Cellular Force Generation |
| title_full | Chemo-Mechanical Factors That Limit Cellular Force Generation |
| title_fullStr | Chemo-Mechanical Factors That Limit Cellular Force Generation |
| title_full_unstemmed | Chemo-Mechanical Factors That Limit Cellular Force Generation |
| title_short | Chemo-Mechanical Factors That Limit Cellular Force Generation |
| title_sort | chemo mechanical factors that limit cellular force generation |
| topic | cell mechanobiology focal adhesions traction forces actin-myosin contractility substrate stiffness |
| url | https://www.frontiersin.org/articles/10.3389/fphy.2022.831776/full |
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