Cell contact guidance via sensing anisotropy of network mechanical resistance

Thrivikraman, Greeshma; Jagiełło, Alicja; Lai, Victor K.; Johnson, Sharon L.; Keating, Mark T.; Nelson, Alexander T; Schultz, Billianne; Wang, Connie M.; Levine, Alex; Botvinick, Elliot L.; Tranquillo, Robert T.

doi:10.1073/pnas.2024942118

Cited by 42 publications

(46 citation statements)

References 59 publications

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“…As noted previously, it was recently demonstrated that human dermal fibroblasts exhibit stronger contact guidance in gels that possess a larger anisotropy of mechanical resistance [8]. In that study, network mechanical resistance was measured using active microrheology, the oscillation of 5 µm microspheres entrapped in the network.…”

Section: Discussionmentioning

confidence: 87%

“…While fibrin and collagen gels share many similarities as highly hydrated fibrillar networks, and fibroblasts exhibit contact guidance in both when aligned [8,29], they are not identical in terms of detailed geometrical factors, such as fibril diameter, density and connectivity. Thus, it is notable that this model predicts quantitative differences with varied fibre mechanical response (nonlinear stiffening parameter, B ) and different fibre connectivity (Delaunay versus Voronoi), but the qualitative trends of S with Ω xx are similar.…”

Section: Discussionmentioning

confidence: 99%

“…Other hypotheses proposed for contact guidance can now also be explored using this model, for example, contact guidance results from anisotropic proteolysis, motivated by the finding that collagen fibrils in tension are more resistant to proteolysis [44], although this mechanism is not distinct from the three stated above and appears not to be important for the system recently studied [8]. Conversely, if a Delaunay or Voronoi network of elastic fibres that obey the fibre mechanical behaviour assumed in this model can be created, it might allow the relative importance of pseudopod protrusion force and pseudopod retraction force to be parsed.…”

Section: Discussionmentioning

confidence: 99%

“…

Figure 1Illustration of Dunn's hypotheses for the sensing mechanism of cell contact guidance in aligned fibrils, adapted from Thrivikraman et al . 2021 [8]. A cell with two pseudopods is shown in an aligned fibre network.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, an approach was developed based on photo-cross-linking of magnetically aligned fibrin gels that decoupled mechanical resistance anisotropy from adhesion and porosity anisotropy and demonstrated that human dermal fibroblasts exhibit stronger contact guidance in gels that possess a larger anisotropy of mechanical resistance [8]. Despite being a significant advance, this study shed no light on whether the cells respond to anisotropy of adhesion or porosity, or which of the three simultaneous anisotropies presents the dominant signal for contact guidance.…”

Section: Introductionmentioning

confidence: 99%

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Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural–mechanical model

Bersie-Larson

Lai

Dhume

et al. 2022

J. R. Soc. Interface.

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Despite its importance in physiological processes and tissue engineering, the mechanism underlying cell contact guidance in an aligned fibrillar network has defied elucidation due to multiple interdependent signals that such a network presents to cells, namely, anisotropy of adhesion, porosity and mechanical behaviour. A microstructural–mechanical model of fibril networks was used to assess the relative magnitudes of these competing signals in networks of varied alignment strength based on idealized cylindrical pseudopods projected into the aligned and orthogonal directions and computing the anisotropy of metrics chosen for adhesion, porosity and mechanical behaviour: cylinder–fibre contact area for adhesion, persistence length of pores for porosity and total force to displace fibres from the cylindrical volume as well as network stiffness experienced upon cylinder retraction for mechanical behaviour. The signals related to mechanical anisotropy are substantially higher than adhesion and porosity anisotropy, especially at stronger network alignments, although their signal to noise (S/N) values are substantially lower. The former finding is consistent with a recent report that fibroblasts can sense fibril alignment via anisotropy of network mechanical resistance, and the model reveals this can be due to either mechanical resistance to pseudopod protrusion or retraction given their signal and S/N values are similar.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural–mechanical model

Bersie-Larson

Lai

Dhume

et al. 2022

J. R. Soc. Interface.

Self Cite

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Physical and Soluble Cues Enhance Tendon Progenitor Cell Invasion into Injectable Synthetic Hydrogels

Kent

Said

Busch

et al. 2022

Adv Funct Materials

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Synthetic hydrogels represent an exciting avenue in the field of regenerative biomaterials given their injectability, orthogonally tunable mechanical properties, and potential for modular inclusion of cellular cues. Separately, recent advances in soluble factor release technology have facilitated control over the soluble milieu in cell microenvironments via tunable microparticles. A composite hydrogel incorporating both of these components can robustly mediate tendon healing following a single injection. Here, a synthetic hydrogel system with encapsulated electrospun fiber segments and a novel microgel‐based soluble factor delivery system achieves precise control over topographical and soluble features of an engineered microenvironment, respectively. It is demonstrated that three‐dimensional migration of tendon progenitor cells can be enhanced via combined mechanical, topographical, and microparticle‐delivered soluble cues in both a tendon progenitor cell spheroid model and an ex vivo murine Achilles tendon model. These results indicate that fiber reinforced hydrogels can drive the recruitment of endogenous progenitor cells relevant to the regeneration of tendon and, likely, a broad range of connective tissues.

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Construction of a Curcumin‐Loaded PLLA/PCL Micro‐Nano Conjugated Fibrous Membrane to Synergistically Prevent Postoperative Adhesion From Multiple Perspectives

Liao,

Li,

Yang

et al. 2024

Adv Funct Materials

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Postoperative adhesion (POA) has emerged as a prevalent clinical challenge in soft tissue repair, emphasizing the critical need for preventive measures. However, the complex POA development process makes POA prevention from a single aspect insufficient. Hence, a curcumin‐loaded poly‐L‐lactic acid‐poly (caprolactone) micro‐nano conjugated fibrous membrane (PAPC MCFM (cur)) is engineered to synergistically prevent POA from multiple perspectives, in which poly (caprolactone) (PCL) nanofibers (118 ± 12 nm) with low orientation traverse the oriented poly‐L‐lactic acid (PLLA) microfibers (2.0 ± 0.3 µm). The PAPC MCFM not only significantly improves the mechanical properties of the anisotropic fibrous membrane (AIFM) that the modulus of elasticity and the tensile strength in the direction vertical to microfiber orientation increase by 4.5 and 13.0 times, respectively, but also can further enhance the “contact guidance effect” of AIFM, i.e., hindering fibroblast adhesion, proliferation, and differentiation to myofibroblast through inhibiting integrin β1 activation, vinculin expression and focal adhesion (FA) formation, and the nuclear localization activation of yes‐associated protein (YAP). Except for these effects, PAPC MCFM loading with 2.5 mg mL−1 curcumin can further prevent POA by delivering anti‐inflammatory, antioxidant, and antibacterial properties, and by suppressing fibrosis through decreased transforming growth factor‐β1(TGF‐β1) expression, showing effective POA prevention in rat abdominal cavity and rabbit dura mater models.

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Cell contact guidance via sensing anisotropy of network mechanical resistance

Cited by 42 publications

References 59 publications

Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural–mechanical model

Elucidating the signal for contact guidance contained in aligned fibrils with a microstructural–mechanical model

Physical and Soluble Cues Enhance Tendon Progenitor Cell Invasion into Injectable Synthetic Hydrogels

Construction of a Curcumin‐Loaded PLLA/PCL Micro‐Nano Conjugated Fibrous Membrane to Synergistically Prevent Postoperative Adhesion From Multiple Perspectives

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