scholarly journals A Dynamic Stochastic Model of Frequency-Dependent Stress Fiber Alignment Induced by Cyclic Stretch

Author(s):  
Hui-Ju Hsu ◽  
Chin-Fu Lee ◽  
Roland Kaunas

Actin stress fibers (SFs) are bundles of actin filaments anchored at each end via focal adhesions. Myosin-generated contraction leads to the development of tension, which extends SFs beyond their unloaded lengths. In human aortic ECs, the level of SF extension is maintained at a set-point level of ∼1.10 (1). SFs are also dynamic structures and their continuous assembly and disassembly is critical to cellular functions involving changes in cell shape. Further, deformation of the extracellular matrix perturbs SF extension, leading to compensatory responses such as the gradual alignment of SFs perpendicular to the principal direction of cyclic stretch. The extent of cell alignment has been shown to depend on the pattern of matrix stretch; however, it is unclear how cells distinguish between different patterns of stretch to determine their unique responses.

Author(s):  
Yunfeng Yang ◽  
Kazuaki Nagayama ◽  
Takeo Matsumoto

Stress fibers (SFs) play essential roles in various cellular functions such as cell movement, shape maintenance and cell division [1]. One of their key features is that they dynamically change their structures in response to mechanical environment to which they are exposed [2]. For example, cultured endothelial cells exposed to cyclic stretch preferentially reorganize their actin stress fibers to the direction in which the strain magnitude of the fibers become minimum [3].


2013 ◽  
Vol 24 (6) ◽  
pp. 768-784 ◽  
Author(s):  
Rocio G. Valencia ◽  
Gernot Walko ◽  
Lubomir Janda ◽  
Jirka Novacek ◽  
Eva Mihailovska ◽  
...  

The transition of microtubules (MTs) from an assembled to a disassembled state plays an essential role in several cellular functions. While MT dynamics are often linked to those of actin filaments, little is known about whether intermediate filaments (IFs) have an influence on MT dynamics. We show here that plectin 1c (P1c), one of the multiple isoforms of the IF-associated cytolinker protein plectin, acts as an MT destabilizer. We found that MTs in P1c-deficient (P1c−/−) keratinocytes are more resistant toward nocodazole-induced disassembly and display increased acetylation. In addition, live imaging of MTs in P1c−/−, as well as in plectin-null, cells revealed decreased MT dynamics. Increased MT stability due to P1c deficiency led to changes in cell shape, increased velocity but loss of directionality of migration, smaller-sized focal adhesions, higher glucose uptake, and mitotic spindle aberrations combined with reduced growth rates of cells. On the basis of ex vivo and in vitro experimental approaches, we suggest a mechanism for MT destabilization in which isoform-specific binding of P1c to MTs antagonizes the MT-stabilizing and assembly-promoting function of MT-associated proteins through an inhibitory function exerted by plectin's SH3 domain. Our results open new perspectives on cytolinker-coordinated IF-MT interaction and its physiological significance.


Author(s):  
Benjamin W. Scandling ◽  
Jia Gou ◽  
Jessica Thomas ◽  
Jacqueline Xuan ◽  
Chuan Xue ◽  
...  

Many cells in the body experience cyclic mechanical loading, which can impact cellular processes and morphology. In vitro studies often report that cells reorient in response to cyclic stretch of their substrate. To explore cellular mechanisms involved in this reorientation, a computational model was developed by utilizing the previous computational models of the actin-myosin-integrin motor-clutch system developed by others. The computational model predicts that under most conditions, actin bundles align perpendicular to the direction of applied cyclic stretch, but under specific conditions, such as low substrate stiffness, actin bundles align parallel to the direction of stretch. The model also predicts that stretch frequency impacts the rate of reorientation, and that proper myosin function is critical in the reorientation response. These computational predictions are consistent with reports from the literature and new experimental results presented here. The model suggests that the impact of different stretching conditions (stretch type, amplitude, frequency, substrate stiffness, etc.) on the direction of cell alignment can largely be understood by considering their impact on cell-substrate detachment events, specifically whether detachment occurs during stretching or relaxing of the substrate.


Nano LIFE ◽  
2014 ◽  
Vol 04 (01) ◽  
pp. 1450002 ◽  
Author(s):  
Qingsu Cheng ◽  
Greg M. Harris ◽  
Marc-Olivier Blais ◽  
Katy Rutledge ◽  
Ehsan Jabbarzadeh

Stem cells offer a promising tool in tissue engineering strategies, as their differentiated derivatives can be used to reconstruct most biological tissues. These approaches rely on controlling the biophysical cues that tune the ultimate fate of cells. In this context, significant effort has gone to parse out the role of conflicting matrix-elicited signals (e.g., topography and elasticity) in regulation of macroscopic characteristics of cells (e.g., shape and polarity). A critical hurdle, however, lies in our inability to recapitulate the nanoscale spatiotemporal pattern of these signals. The study presented in this manuscript took an initial step to overcome this challenge by developing a carbon nanotube (CNT)-based substrate for nanoresolution control of focal adhesion formation and cell alignment. The utility of this system was studied using human umbilical vascular endothelial cells (HUVECs) and human embryonic stem cells (hESCs) at a single cell level. Our results demonstrated the ability to control cell orientation by merely controlling the alignment of focal adhesions at a nanoscale size. Our long-term vision is to use these nanoengineered substrates to mimic cell orientation in earlier development and explore the role of polarity in asymmetric division and lineage specification of dividing cells.


Author(s):  
Ji Lin ◽  
Xiaokeng Li ◽  
Jun Yin ◽  
Jin Qian

The directional alignment and outgrowth of neurons is a critical step of nerve regeneration and functional recovery of nerve systems, where neurons are exposed to a complex mechanical environment with subcellular structures such as stress fibers and focal adhesions acting as the key mechanical transducer. In this paper, we investigate the effects of cyclic stretch on neuron reorientation and axon outgrowth with a feasible stretching device that controls stretching amplitude and frequency. Statistical results indicate an evident frequency and amplitude dependence of neuron reorientation, that is, neurons tend to align away from stretch direction when stretching amplitude and frequency are large enough. On the other hand, axon elongation under cyclic stretch is very close to the reference case where neurons are not stretched. A mechanochemical framework is proposed by connecting the evolution of cellular configuration to the microscopic dynamics of subcellular structures, including stress fiber, focal adhesion, and microtubule, yielding theoretical predictions that are consistent with the experimental observations. The theoretical work provides an explanation of the neuron’s mechanical response to cyclic stretch, suggesting that the contraction force generated by stress fiber plays an essential role in both neuron reorientation and axon elongation. This combined experimental and theoretical study on stretch-induced neuron reorientation may have potential applications in neurodevelopment and neuron regeneration.


1996 ◽  
Vol 16 (5) ◽  
pp. 1896-1908 ◽  
Author(s):  
N Harden ◽  
J Lee ◽  
H Y Loh ◽  
Y M Ong ◽  
I Tan ◽  
...  

Changes in cell morphology are essential in the development of a multicellular organism. The regulation of the cytoskeleton by the Rho subfamily of small GTP-binding proteins is an important determinant of cell shape. The Rho subfamily has been shown to participate in a variety of morphogenetic processes during Drosophila melanogaster development. We describe here a Drosophila homolog, DPAK, of the serine/threonine kinase PAK, a protein which is a target of the Rho subfamily proteins Rac and Cdc42. Rac, Cdc42, and PAK have previously been implicated in signaling by c-Jun amino-terminal kinases. DPAK bound to activated (GTP-bound) Drosophila Rac (DRacA) and Drosophila Cdc42. Similarities in the distributions of DPAK, integrin, and phosphotyrosine suggested an association of DPAK with focal adhesions and Cdc42- and Rac-induced focal adhesion-like focal complexes. DPAK was elevated in the leading edge of epidermal cells, whose morphological changes drive dorsal closure of the embryo. We have previously shown that the accumulation of cytoskeletal elements initiating cell shape changes in these cells could be inhibited by expression of a dominant-negative DRacA transgene. We show that leading-edge epidermal cells flanking segment borders, which express particularly large amounts of DPAK, undergo transient losses of cytoskeletal structures during dorsal closure. We propose that DPAK may be regulating the cytoskeleton through its association with focal adhesions and focal complexes and may be participating with DRacA in a c-Jun amino-terminal kinase signaling pathway recently demonstrated to be required for dorsal closure.


2015 ◽  
Vol 21 (9) ◽  
pp. 881-888 ◽  
Author(s):  
Christophe Chaubaroux ◽  
Fabienne Perrin-Schmitt ◽  
Bernard Senger ◽  
Loïc Vidal ◽  
Jean-Claude Voegel ◽  
...  

Biomaterials ◽  
2011 ◽  
Vol 32 (8) ◽  
pp. 2043-2051 ◽  
Author(s):  
Andrew D. Rape ◽  
Wei-hui Guo ◽  
Yu-li Wang

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