A time-dependent phenomenological model for cell mechano-sensing

Borau, Carlos; Kamm, Roger D.; García-Aznar, J.M.

doi:10.1007/s10237-013-0508-x

Cited by 15 publications

(8 citation statements)

References 35 publications

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“…(c) A conceptual diagram of a continuum model of a cell and its mechanical interaction with the ECM. The model incorporates the role of ECM stiffness in the traction forces felt at the cell adhesions (Reprinted with permission from Ref . Copyright 2013 Springer).…”

Section: Measurements and Models Of The Contribution Of Adhesions Andmentioning

confidence: 99%

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

Rajagopal

Holmes

Lee

2017

WIREs Mechanisms of Disease

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Cellular cytoskeletal mechanics plays a major role in many aspects of human health from organ development to wound healing, tissue homeostasis and cancer metastasis. We summarize the state‐of‐the‐art techniques for mathematically modeling cellular stiffness and mechanics and the cytoskeletal components and factors that regulate them. We highlight key experiments that have assisted model parameterization and compare the advantages of different models that have been used to recapitulate these experiments. An overview of feed‐forward mechanisms from signaling to cytoskeleton remodeling is provided, followed by a discussion of the rapidly growing niche of encapsulating feedback mechanisms from cytoskeletal and cell mechanics to signaling. We discuss broad areas of advancement that could accelerate research and understanding of cellular mechanobiology. A precise understanding of the molecular mechanisms that affect cell and tissue mechanics and function will underpin innovations in medical device technologies of the future. WIREs Syst Biol Med 2018, 10:e1407. doi: 10.1002/wsbm.1407This article is categorized under: Models of Systems Properties and Processes > Mechanistic ModelsPhysiology > Mammalian Physiology in Health and DiseaseModels of Systems Properties and Processes > Cellular Models

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Section: Measurements and Models Of The Contribution Of Adhesions Andmentioning

confidence: 99%

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

Rajagopal

Holmes

Lee

2017

WIREs Mechanisms of Disease

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“…In particular, the extended model predicts that cell migration is linked to the deformability of the substrate, where cells are more likely to migrate to regions that produce higher cellular stresses. These results have been built on and generalized by incorporating rate-dependent effects while simultaneously considering extracellular rigidity (Borau, Kamm, & García-Aznar, 2014). The one-dimensional phenomenological model used a three-spring configuration to predict the mechanosensing behavior of single cells.…”

Section: Modeling Approaches At the Cellular Scalementioning

confidence: 99%

Exploring cardiac form and function: A length‐scale computational biology approach

Sherman

Grosberg

2019

WIREs Mechanisms of Disease

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The ability to adequately pump blood throughout the body is the result of tightly regulated feedback mechanisms that exist across many spatial scales in the heart. Diseases which impede the function at any one of the spatial scales can cause detrimental cardiac remodeling and eventual heart failure. An overarching goal of cardiac research is to use engineered heart tissue in vitro to study the physiology of diseased heart tissue, develop cell replacement therapies, and explore drug testing applications. A commonality within the field is to manipulate the flow of mechanical signals across the various spatial scales to direct self-organization and build functional tissue. Doing so requires an understanding of how chemical, electrical, and mechanical cues can be used to alter the cellular microenvironment. We discuss how mathematical models have been used in conjunction with experimental techniques to explore various structure-function relations that exist across numerous spatial scales. We highlight how a systems biology approach can be employed to recapitulate in vivo characteristics in vitro at the tissue, cell, and subcellular scales. Specific focus is placed on the interplay between experimental and theoretical approaches. Various modeling methods are showcased to demonstrate the breadth and power afforded to the systems biology approach. An overview of modeling methodologies exemplifies how the strengths of different scientific disciplines can be used to supplement and/or inspire new avenues of experimental exploration. This article is categorized under: Models of Systems Properties and Processes > Mechanistic Models Models of Systems Properties and Processes > Cellular Models Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models K E Y W O R D S cardiac modeling, deterministic models, model validation

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“…Finally, inclusion of active remodeling of the nuclear lamina and the cytoskeleton would elucidate the mechanical interplay between the two cell compartments. Such an approach would enable the modeling of dynamic mechanotransduction processes, similar to the benefits provided by cell models incorporating active cytoskeletal contraction [214,219,220,222,[225][226][227]230,231,[249][250][251][252][253][254][255]. Furthermore, these models could capture the influence of load-induced nuclear remodeling on mechanotransduction processes that occur within the cytoplasm and plasma membrane.…”

Section: Mathematical Models Of Nuclear Mechanotransductionmentioning

confidence: 99%

The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction

Szczesny

Mauck

2017

Journal of Biomechanical Engineering

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Biophysical stimuli presented to cells via microenvironmental properties (e.g., alignment and stiffness) or external forces have a significant impact on cell function and behavior. Recently, the cell nucleus has been identified as a mechanosensitive organelle that contributes to the perception and response to mechanical stimuli. However, the specific mechanotransduction mechanisms that mediate these effects have not been clearly established. Here, we offer a comprehensive review of the evidence supporting (and refuting) three hypothetical nuclear mechanotransduction mechanisms: physical reorganization of chromatin, signaling at the nuclear envelope, and altered cytoskeletal structure/tension due to nuclear remodeling. Our goal is to provide a reference detailing the progress that has been made and the areas that still require investigation regarding the role of nuclear mechanotransduction in cell biology. Additionally, we will briefly discuss the role that mathematical models of cell mechanics can play in testing these hypotheses and in elucidating how biophysical stimulation of the nucleus drives changes in cell behavior. While force-induced alterations in signaling pathways involving lamina-associated polypeptides (LAPs) (e.g., emerin and histone deacetylase 3 (HDAC3)) and transcription factors (TFs) located at the nuclear envelope currently appear to be the most clearly supported mechanism of nuclear mechanotransduction, additional work is required to examine this process in detail and to more fully test alternative mechanisms. The combination of sophisticated experimental techniques and advanced mathematical models is necessary to enhance our understanding of the role of the nucleus in the mechanotransduction processes driving numerous critical cell functions.

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A time-dependent phenomenological model for cell mechano-sensing

Cited by 15 publications

References 35 publications

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

Exploring cardiac form and function: A length‐scale computational biology approach

The Nuclear Option: Evidence Implicating the Cell Nucleus in Mechanotransduction

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