Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks
Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biologica...
| Main Authors: | , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Public Library of Science
2013
|
| Online Access: | http://hdl.handle.net/1721.1/76597 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826214276925227008 |
|---|---|
| author | Borau, Carlos Kamm, Roger Dale |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Borau, Carlos Kamm, Roger Dale |
| author_sort | Borau, Carlos |
| collection | MIT |
| description | Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells. |
| first_indexed | 2024-09-23T16:03:03Z |
| format | Article |
| id | mit-1721.1/76597 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:03:03Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/765972022-10-02T05:58:11Z Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks Borau, Carlos Kamm, Roger Dale Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Borau, Carlos Kamm, Roger Dale Cells modulate themselves in response to the surrounding environment like substrate elasticity, exhibiting structural reorganization driven by the contractility of cytoskeleton. The cytoskeleton is the scaffolding structure of eukaryotic cells, playing a central role in many mechanical and biological functions. It is composed of a network of actins, actin cross-linking proteins (ACPs), and molecular motors. The motors generate contractile forces by sliding couples of actin filaments in a polar fashion, and the contractile response of the cytoskeleton network is known to be modulated also by external stimuli, such as substrate stiffness. This implies an important role of actomyosin contractility in the cell mechano-sensing. However, how cells sense matrix stiffness via the contractility remains an open question. Here, we present a 3-D Brownian dynamics computational model of a cross-linked actin network including the dynamics of molecular motors and ACPs. The mechano-sensing properties of this active network are investigated by evaluating contraction and stress in response to different substrate stiffness. Results demonstrate two mechanisms that act to limit internal stress: (i) In stiff substrates, motors walk until they exert their maximum force, leading to a plateau stress that is independent of substrate stiffness, whereas (ii) in soft substrates, motors walk until they become blocked by other motors or ACPs, leading to submaximal stress levels. Therefore, this study provides new insights into the role of molecular motors in the contraction and rigidity sensing of cells. 2013-01-24T18:13:04Z 2013-01-24T18:13:04Z 2012-11 2012-08 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/76597 Borau, Carlos et al. “Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks.” Ed. Wilbur Lam. PLoS ONE 7.11 (2012): e49174. https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1371/journal.pone.0049174 PLoS ONE Creative Commons Attribution http://creativecommons.org/licenses/by/2.5/ application/pdf Public Library of Science PLoS |
| spellingShingle | Borau, Carlos Kamm, Roger Dale Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title | Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title_full | Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title_fullStr | Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title_full_unstemmed | Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title_short | Dynamic Mechanisms of Cell Rigidity Sensing: Insights from a Computational Model of Actomyosin Networks |
| title_sort | dynamic mechanisms of cell rigidity sensing insights from a computational model of actomyosin networks |
| url | http://hdl.handle.net/1721.1/76597 https://orcid.org/0000-0002-7232-304X |
| work_keys_str_mv | AT boraucarlos dynamicmechanismsofcellrigiditysensinginsightsfromacomputationalmodelofactomyosinnetworks AT kammrogerdale dynamicmechanismsofcellrigiditysensinginsightsfromacomputationalmodelofactomyosinnetworks |