Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics

Rens, Elisabeth G.; Merks, Roeland

doi:10.1016/j.isci.2020.101488

Cited by 74 publications

(70 citation statements)

References 112 publications

(213 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With respect to cell shape, on all substrates, the cells exhibited a round morphology, whilst cells have been reported to be of round morphology on low bloom index hydrogels and of elongated morphology on high bloom index hydrogels [57][58][59]. We attribute this indifference in cell shape between the different gelatin preparations to residual endotoxins.…”

Section: Discussionmentioning

confidence: 82%

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

Korntner

Olijve³

et al. 2021

Biomolecules

View full text Add to dashboard Cite

In the medical device sector, bloom index and residual endotoxins should be controlled, as they are crucial regulators of the device’s physicochemical and biological properties. It is also imperative to identify a suitable crosslinking method to increase mechanical integrity, without jeopardising cellular functions of gelatin-based devices. Herein, gelatin preparations with variable bloom index and endotoxin levels were used to fabricate non-crosslinked and polyethylene glycol succinimidyl glutarate crosslinked gelatin scaffolds, the physicochemical and biological properties of which were subsequently assessed. Gelatin preparations with low bloom index resulted in hydrogels with significantly (p < 0.05) lower compression stress, elastic modulus and resistance to enzymatic degradation, and significantly higher (p < 0.05) free amine content than gelatin preparations with high bloom index. Gelatin preparations with high endotoxin levels resulted in films that induced significantly (p < 0.05) higher macrophage clusters than gelatin preparations with low endotoxin level. Our data suggest that the bloom index modulates the physicochemical properties, and the endotoxin content regulates the biological response of gelatin biomaterials. Although polyethylene glycol succinimidyl glutarate crosslinking significantly (p < 0.05) increased compression stress, elastic modulus and resistance to enzymatic degradation, and significantly (p < 0.05) decreased free amine content, at the concentration used, it did not provide sufficient structural integrity to support cell culture. Therefore, the quest for the optimal gelatin crosslinker continues.

show abstract

Section: Discussionmentioning

confidence: 82%

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

Korntner

Olijve³

et al. 2021

Biomolecules

View full text Add to dashboard Cite

show abstract

“…Accordingly, in soft matrices, weak RhoA-driven cytoskeletal tensile forces fail to stabilize cell adhesions, rendering non-effective cell spread. This negatively regulates the recruitment of integrins and induces integrin endocytosis and subsequent lysosomal degradation ( Figure 3 ) [ 102 , 106 ]. Therefore, ECM stiffness and densification modulate the size and number of FAs of cells immersed in 3D matrices.…”

Section: Three-dimensional (3d) Ecm-mimicking Scaffolds: Sensing mentioning

confidence: 99%

Modeling the Mechanobiology of Cancer Cell Migration Using 3D Biomimetic Hydrogels

Morales

Cortés-Domínguez

Ortiz‐de‐Solórzano

2021

Gels

View full text Add to dashboard Cite

Understanding how cancer cells migrate, and how this migration is affected by the mechanical and chemical composition of the extracellular matrix (ECM) is critical to investigate and possibly interfere with the metastatic process, which is responsible for most cancer-related deaths. In this article we review the state of the art about the use of hydrogel-based three-dimensional (3D) scaffolds as artificial platforms to model the mechanobiology of cancer cell migration. We start by briefly reviewing the concept and composition of the extracellular matrix (ECM) and the materials commonly used to recreate the cancerous ECM. Then we summarize the most relevant knowledge about the mechanobiology of cancer cell migration that has been obtained using 3D hydrogel scaffolds, and relate those discoveries to what has been observed in the clinical management of solid tumors. Finally, we review some recent methodological developments, specifically the use of novel bioprinting techniques and microfluidics to create realistic hydrogel-based models of the cancer ECM, and some of their applications in the context of the study of cancer cell migration.

show abstract

“…Explicit descriptions of cell-matrix adhesions were recently introduced into this framework [54] to describe tension-dependent growth of focal adhesions. In our future work, this methodology will allow us to study the mechanisms by which substrate compliance affects lymphocyte motility.…”

Section: Interplay Between Cytoskeleton and Substratementioning

confidence: 99%

Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics

Sire

Dupré

Théraulaz

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Lymphocytes have been described to perform different motility patterns such as Brownian random walks, persistent random walks, and Lévy walks. Depending on the conditions, such as confinement or the distribution of target cells, either Brownian or Lévy walks lead to more efficient interaction with the targets. The diversity of these motility patterns may be explained by an adaptive response to the surrounding extracellular matrix (ECM). Indeed, depending on the ECM composition, lymphocytes either display a floating motion without attaching to the ECM, or sliding and stepping motion with respectively continuous or discontinuous attachment to the ECM, or pivoting behaviour with sustained attachment to the ECM. Moreover, on the long term, lymphocytes either perform a persistent random walk or a Brownian-like movement depending on the ECM composition. How the ECM affects cell motility is still incompletely understood. Here, we integrate essential mechanistic details of the lymphocyte-matrix adhesions and lymphocyte intrinsic cytoskeletal induced cell propulsion into a Cellular Potts model (CPM). We show that the combination of \textit{de novo} cell-matrix adhesion formation, adhesion growth and shrinkage, adhesion rupture, and feedback of adhesions onto cell propulsion recapitulates multiple lymphocyte behaviours, for different lymphocyte subsets and various substrates. With an increasing attachment area and increased adhesion strength, the cells' speed and persistence decreases. Additionally, the model can predict short-term persistent with long-term subdiffusive motility, showing a pivoting motion. For small adhesion areas, we observe that the spatial distribution of adhesions influences cell motility. Small adhesions at the front allow for more persistent motion than larger clusters at the back, despite a similar total adhesion area. In conclusion, we present an integrated framework to simulate the effects of ECM proteins on cell-matrix adhesion dynamics. The model reveals a sufficient set of principles explaining the plasticity of lymphocyte motility.

show abstract

Cell Shape and Durotaxis Explained from Cell-Extracellular Matrix Forces and Focal Adhesion Dynamics

Cited by 74 publications

References 112 publications

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

The Influence of Bloom Index, Endotoxin Levels and Polyethylene Glycol Succinimidyl Glutarate Crosslinking on the Physicochemical and Biological Properties of Gelatin Biomaterials

Modeling the Mechanobiology of Cancer Cell Migration Using 3D Biomimetic Hydrogels

Computational modelling of cell motility modes emerging from cell-matrix adhesion dynamics

Contact Info

Product

Resources

About