Kinetic model for lamellipodal actin-integrin 'clutch' dynamics

Macdonald, Alice; Horwitz, Alan Rick; Lauffenburger, Douglas A.

doi:10.4161/cam.2.2.6210

Cited by 42 publications

(49 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Force transmission through such a dynamic interface can be modeled by considering a population of dynamic bonds formed between a moving and stationary interface with individual bonds undergoing cycles of attachment and force-assisted detachment. Thus, the dynamics of bond association/dissociation facilitate F-actin motion and force transmission simultaneously [57,59-61]. These models are consistent with the observed relationships between F-actin flow speed and traction force [60,61]; at high retrograde flow rates, force transmission is limited by bond breakage whereas at low rates, the magnitude of displacement or force within the actin cytoskeleton is limiting.…”

Section: How Can a Dynamic Cytoskeleton Sustain Mechanical Load?mentioning

confidence: 53%

“…These models are consistent with the observed relationships between F-actin flow speed and traction force [60,61]; at high retrograde flow rates, force transmission is limited by bond breakage whereas at low rates, the magnitude of displacement or force within the actin cytoskeleton is limiting. Furthermore, these models have elucidated how such a dynamic clutch could facilitate adhesion assembly [59] and mechanosensing [57]. This mechanism allows for both the build-up of tension at locations of rapid F-actin flow to promote adhesion assembly and reduce tension at sites of low F-actin flow to promote adhesion disassembly.…”

Section: How Can a Dynamic Cytoskeleton Sustain Mechanical Load?mentioning

confidence: 99%

See 1 more Smart Citation

Conserved F-actin dynamics and force transmission at cell adhesions

Maruthamuthu

Aratyn-Schaus

Gardel

2010

Current Opinion in Cell Biology

View full text Add to dashboard Cite

Abstract/Summary Adhesions are a central mechanism by which cells mechanically interact with the surrounding extracellular matrix (ECM) and neighboring cells. In both cell-ECM and cell-cell adhesions, forces generated within the actin cytoskeleton are transmitted to the surrounding environment and are essential for numerous morphogenic processes. Despite differences in many molecular components that regulate cell-cell and cell-ECM adhesions, the roles of F-actin dynamics and mechanical forces in adhesion regulation are surprisingly similar. Moreover, force transmission at adhesions occurs concomitantly with dynamic F-actin; proteins comprising the adhesion of F-actin to the plasma membrane must accommodate this movement while still facilitating force transmission. Thus, despite different molecular architectures, integrin and cadherin-mediated adhesions operate with common biophysical characteristics to transmit and respond to mechanical forces in a multicellular tissue.

show abstract

Section: How Can a Dynamic Cytoskeleton Sustain Mechanical Load?mentioning

confidence: 53%

Section: How Can a Dynamic Cytoskeleton Sustain Mechanical Load?mentioning

confidence: 99%

Conserved F-actin dynamics and force transmission at cell adhesions

Maruthamuthu

Aratyn-Schaus

Gardel

2010

Current Opinion in Cell Biology

View full text Add to dashboard Cite

show abstract

“…A whole cell actomyosin and adhesion model has also been presented, but does not include stiffness sensitivity, load and fail dynamics, or the force-velocity relationship 30 . Aspects of these and other models such as actin dynamics 30,31 , membrane tension 32,33 , and adhesion formation and maturation 2,34,35 could be incorporated to provide further insight into actomyosin, adhesion complex, and membrane behavior. For example, the individual clutch molecules could be included, each with its own kinetic rates and spring constant to better describe adhesion formation and maturation.…”

Section: Discussionmentioning

confidence: 99%

Master Equation-Based Analysis of a Motor-Clutch Model for Cell Traction Force

Bangasser

Odde

2013

Cel. Mol. Bioeng.

View full text Add to dashboard Cite

Microenvironmental mechanics play an important role in determining the morphology, traction, migration, proliferation, and differentiation of cells. A stochastic motor-clutch model has been proposed to describe this stiffness sensitivity. In this work, we present a master equation-based ordinary differential equation (ODE) description of the motor-clutch model, from which we derive an analytical expression to for a cell’s optimum stiffness (i.e. the stiffness at which the traction force is maximal). This analytical expression provides insight into the requirements for stiffness sensing by establishing fundamental relationships between the key controlling cell-specific parameters. We find that the fundamental controlling parameters are the numbers of motors and clutches (constrained to be nearly equal), and the time scale of the on-off kinetics of the clutches (constrained to favor clutch binding over clutch unbinding). Both the ODE solution and the analytical expression show good agreement with Monte Carlo motor-clutch output, and reduce computation time by several orders of magnitude, which potentially enables long time scale behaviors (hours-days) to be studied computationally in an efficient manner. The ODE solution and the analytical expression may be incorporated into larger scale models of cellular behavior to bridge the gap from molecular time scales to cellular and tissue time scales.

show abstract

“…However, molecular-scale spatial parameters that specify FA nanoscale organization have been difficult to access experimentally. Nevertheless, these are essential to understand how mechanosensitivity arises within such complex molecular machines (11)(12)(13)(14)(15).…”

mentioning

confidence: 99%

Talin determines the nanoscale architecture of focal adhesions

Liu

Wang

Goh

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

172

169

View full text Add to dashboard Cite

Insight into how molecular machines perform their biological functions depends on knowledge of the spatial organization of the components, their connectivity, geometry, and organizational hierarchy. However, these parameters are difficult to determine in multicomponent assemblies such as integrin-based focal adhesions (FAs). We have previously applied 3D superresolution fluorescence microscopy to probe the spatial organization of major FA components, observing a nanoscale stratification of proteins between integrins and the actin cytoskeleton. Here we combine superresolution imaging techniques with a protein engineering approach to investigate how such nanoscale architecture arises. We demonstrate that talin plays a key structural role in regulating the nanoscale architecture of FAs, akin to a molecular ruler. Talin diagonally spans the FA core, with its N terminus at the membrane and C terminus demarcating the FA/stress fiber interface. In contrast, vinculin is found to be dispensable for specification of FA nanoscale architecture. Recombinant analogs of talin with modified lengths recapitulated its polarized orientation but altered the FA/stress fiber interface in a linear manner, consistent with its modular structure, and implicating the integrin-talin-actin complex as the primary mechanical linkage in FAs. Talin was found to be ∼97 nm in length and oriented at ∼15°relative to the plasma membrane. Our results identify talin as the primary determinant of FA nanoscale organization and suggest how multiple cellular forces may be integrated at adhesion sites.superresolution microscopy | focal adhesions | talin | mechanobiology | nanoscale architecture C ell adhesion to the ECM is a highly coordinated process that involves ECM-specific recognition by integrin transmembrane receptors, and their aggregation with numerous cytoplasmic proteins into dense supramolecular complexes called focal adhesions (FAs) (1). Actin stress fibers terminate at FAs where actomyosin contractility is transmitted to the ECM, generating traction (2-5). Mechanical tension impinging on each FA is implicated in key steps including the elongation, reinforcement, and maintenance of the FA structures (6). FA mechanotransduction is a major aspect of cellular microenvironment sensing with wide-ranging consequences in physiological and pathological processes (7-10). However, molecular-scale spatial parameters that specify FA nanoscale organization have been difficult to access experimentally. Nevertheless, these are essential to understand how mechanosensitivity arises within such complex molecular machines (11-15).Previously 3D superresolution fluorescence microscopy has unveiled the nanoscale organization of major FA components, whereby a core region of ∼30 nm interposes between the integrin and the actin cytoskeleton along the vertical (z) axis (16). The FA core consists of a membrane-proximal layer that contains signaling proteins such as FAK (focal adhesion kinase) and paxillin, an intermediate zone that contains force-transduction proteins s...

show abstract

Kinetic model for lamellipodal actin-integrin 'clutch' dynamics

Cited by 42 publications

References 43 publications

Conserved F-actin dynamics and force transmission at cell adhesions

Conserved F-actin dynamics and force transmission at cell adhesions

Master Equation-Based Analysis of a Motor-Clutch Model for Cell Traction Force

Talin determines the nanoscale architecture of focal adhesions

Contact Info

Product

Resources

About