Cell shape provides global control of focal adhesion assembly

Chen, Christopher; Alonso, José L.; Ostuni, Emanuele; Whitesides, George M.; Ingber, Donald E.

doi:10.1016/s0006-291x(03)01165-3

Cited by 496 publications

(439 citation statements)

References 23 publications

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“…In previous studies, a larger contact area has been correlated with a higher number of focal adhesions per cell and demonstrated the promotion of osteogenic differentiation via RhoA mediated actin‐myosin generated tension 22, 29. This, however, does not explain our observations where osteogenic differentiation was higher on convex structures compared to flat and concave structures: The number of focal adhesions per cell did not differ significantly between convex and flat structures (Figure 3B) and the F‐actin signal was even lower on convex compared to concave surfaces (Figure 4E,F).…”

Section: Resultsmentioning

confidence: 92%

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

et al. 2016

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Signals from the microenvironment around a cell are known to influence cell behavior. Material properties, such as biochemical composition and substrate stiffness, are today accepted as significant regulators of stem cell fate. The knowledge of how cell behavior is influenced by 3D geometric cues is, however, strongly limited despite its potential relevance for the understanding of tissue regenerative processes and the design of biomaterials. Here, the role of surface curvature on the migratory and differentiation behavior of human mesenchymal stem cells (hMSCs) has been investigated on 3D surfaces with well‐defined geometric features produced by stereolithography. Time lapse microscopy reveals a significant increase of cell migration speed on concave spherical compared to convex spherical structures and flat surfaces resulting from an upward‐lift of the cell body due to cytoskeletal forces. On convex surfaces, cytoskeletal forces lead to substantial nuclear deformation, increase lamin‐A levels and promote osteogenic differentiation. The findings of this study demonstrate a so far missing link between 3D surface curvature and hMSC behavior. This will not only help to better understand the role of extracellular matrix architecture in health and disease but also give new insights in how 3D geometries can be used as a cell‐instructive material parameter in the field of biomaterial‐guided tissue regeneration.

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Section: Resultsmentioning

confidence: 92%

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

et al. 2016

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“…dynamics of focal adhesions, and we propose that this impairment in focal adhesion numbers and lengths, observed on NS, reduces the ability of cells to spread above the threshold required for cell cycle progression and survival. 17,18,26,27 Although lower adhesion numbers and lengths were observed on TS, the percentage of adhesions below 1 mm in length was low, and overall cell shape was not affected.…”

Section: Discussionmentioning

confidence: 89%

“…These measurements might indicate that the lower number and length groupings for the focal adhesions of cells on NS compared to TS could dip below a certain threshold value required for spreading and proliferation on the surface. 17,18 Lower amounts of focal adhesions have also been linked to an increase in cell migration, tying in with the polarized cell morphology. 19 The microtubule network for cells on the three smooth surfaces and TS were clearly defined and extended to all areas of the cell body with no visible influence from the underlying topography.…”

Section: Discussionmentioning

confidence: 99%

Microtopography of metal surfaces influence fibroblast growth by modifying cell shape, cytoskeleton, and adhesion

Meredith

Eschbach

Riehle

et al. 2007

Journal Orthopaedic Research

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Stainless Steel (SS), titanium (cpTi), and Ti-6Al-7Nb (TAN) are frequently used metals in fracture fixation, which contact not only bone, but also soft tissue. In previous soft tissue cytocompatibility studies, TAN was demonstrated to inhibit cell growth in its ''standard'' microroughened state. To elucidate a possible mechanism for this inhibition, cell area, shape, adhesion, and cytoskeletal integrity was studied. Only minor changes in spreading were observed for cells on electropolished SS, cpTi, and TAN. Cells on ''standard'' cpTi were similarly spread in comparison with electropolished cpTi and TAN, although the topography influenced the cell periphery and also resulted in lower numbers and shorter length of focal adhesions. On ''standard'' microrough TAN, cell spreading was significantly lower than all other surfaces, and cell morphology differed by being more elongated. In addition, focal adhesion numbers and mean length were significantly lower on standard TAN than on all other surfaces, with 80% of the measured adhesions below a 2-mm threshold. Focal adhesion site location and maturation and microtubule integrity were compromised by the presence of protruding b-phase microspikes found solely on the surface of standard TAN. This led us to propose that the impairment of focal adhesion numbers, maturation (length), and cell spreading to a possibly sufficient threshold observed on standard TAN blocks cell cycle progress and eventually cell growth on the surface. We believe, as demonstrated with standard cpTi and TAN, that a difference in surface morphology is influential for controlling cell behavior on implant surfaces.

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“…In addition, the growth of FAs in response to Rho activation appears to be due to an increase of force on the adhesion, because FAs will also grow when physical force is applied to the cell by stretching it [21,22]. Likewise, if force on an adhesion is decreased, the adhesion will disassemble [23,24]. This basic mechanism of reinforcement in response to an increase in force, and release in response to a decrease in force, is a fundamental property of FAs that plays an important role in several physiological processes of the cell such as migration and proliferation.…”

Section: Adhesion and The Development Of Tensionmentioning

confidence: 99%

Focal adhesion kinase as a regulator of cell tension in the progression of cancer

Tilghman¹,

Parsons²

2008

Seminars in Cancer Biology

145

115

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Growing evidence indicates that critical steps in cancer progression such as cell adhesion, migration, and cell cycle progression are regulated by the composition and organization of the microenvironment. The adhesion of cancer cells to components of the microenvironment and the forces transmitted to the cells via the actinomyosin network and the signaling complexes organized within focal adhesions allow cancer cells to sense the local topography of the extracellular matrix and respond efficiently to proximal growth and migration promoting cues. Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is over expressed in a variety of cancers and plays an important role in cell adhesion, migration, and anchorage-dependent growth. In this review, we summarize evidence which implicate FAK in the ability of cells to sense and respond to local forces from the microenvironment through the regulation of adhesion dynamics and actinomyosin contractility, and we discuss the potential roles of FAK as a mechanosensor in the progression of cancer.

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Cell shape provides global control of focal adhesion assembly

Cited by 496 publications

References 23 publications

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

Surface Curvature Differentially Regulates Stem Cell Migration and Differentiation via Altered Attachment Morphology and Nuclear Deformation

Microtopography of metal surfaces influence fibroblast growth by modifying cell shape, cytoskeleton, and adhesion

Focal adhesion kinase as a regulator of cell tension in the progression of cancer

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