Mix and (mis-)match – The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart

Ward, Matthew J.; Iskratsch, Thomas

doi:10.1016/j.bbamcr.2019.01.017

Cited by 39 publications

(68 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DNA origami without any peptides attached were used as a control. An optimum concentration of 2 nM DNA origami was used to achieve a uniform surface coverage of 10 3 DNA origami/µm 2 ( Figure 5). Surfaces were ± passivated with an methoxy PEG silane and blocked with 5% bovine serum albumin to minimise non-specific adhesion.…”

Section: Faraday Discussion Accepted Manuscriptmentioning

confidence: 99%

“…DNA origami were designed to present 6 peptides/EGF along their outer edges, at 60 nm intervals. To demonstrate the versatility of DNA origami substrate nanopatterning, we sought to extend this approach to the investigation of integrin clustering dynamics for primary neonatal rat cardiomyocytes (NRCs), which due to their contractile nature differ from other cell types in adhesion structure and cytoskeletal organisation 10,33 . For this purpose, DNA origami were engineered to present the cyclic RGD (cRGDfC) peptide.…”

Section: Design Of the Arrays And Nanostructuresmentioning

confidence: 99%

“…The contact interface between the ECM and cell-binding domains, depends on the receptors' nanoscale spatial organisation 2,3 and clustering [4][5][6][7] . Integrin-ECM interactions are also regulated by cellular (cytoskeletal) and extracellular forces (such as the passive stiffness of the ECM) that affect the stability of the bonds 1,[8][9][10] . Importantly integrin clustering distributes the forces between the receptor-ligand complexes, increasing the maximum force per bond and enabling further integrin adhesion assembly 4-6, 9, 11 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Probing the nanoscale organisation and multivalency of cell surface receptors: DNA origami nanoarrays for cellular studies with single-molecule control

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Faraday Discussion Accepted Manuscriptmentioning

confidence: 99%

Section: Design Of the Arrays And Nanostructuresmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Probing the nanoscale organisation and multivalency of cell surface receptors: DNA origami nanoarrays for cellular studies with single-molecule control

et al. 2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…fibronectin and laminin), proteoglycans (especially heparan sulfate proteoglycans) and elastin. These molecules interact with cell surface receptors, such as integrins which link the ECM to the internal cytoskeletal network and function also as mechanical sensing and signalling hubs (Awada et al 2016; Baudino et al 2006; Ward and Iskratsch 2019). However, the composition of the ECM is dynamic and changes during development and in disease.…”

Section: Structure Of the Cardiac Ecm And Mechanical Changes In Heartmentioning

confidence: 99%

“…The cells in the heart or vessel walls sense the changes to chemical and mechanical signalling and respond to the restructuring of the ECM by changing their phenotype; e.g. cardiomyocytes become less contractile due to changes in gene expression and myofibrillar organisation (Ward and Iskratsch 2019), while vascular smooth muscle cells can switch from a contractile to a synthetic phenotype that allows them to start migrating or invading into the inner layer of the vessel wall (Hartman et al 2016; McDaniel et al 2007).…”

Section: Introduction (Ie Why Care About Mechanosensing In the Cardmentioning

confidence: 99%

Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing

Sit

Gutmann

Iskratsch

2019

J Muscle Res Cell Motil

Self Cite

View full text Add to dashboard Cite

The stiffness of the cardiovascular environment changes during ageing and in disease and contributes to disease incidence and progression. For instance, increased arterial stiffness can lead to atherosclerosis, while stiffening of the heart due to fibrosis can increase the chances of heart failure. Cells can sense the stiffness of the extracellular matrix through integrin adhesions and other mechanosensitive structures and in response to this initiate mechanosignalling pathways that ultimately change the cellular behaviour. Over the past decades, interest in mechanobiology has steadily increased and with this also our understanding of the molecular basis of mechanosensing and transduction. However, much of our knowledge about the mechanisms is derived from studies investigating focal adhesions in non-muscle cells, which are distinct in several regards from the cell-matrix adhesions in cardiomyocytes (costameres) or vascular smooth muscle cells (dense plaques or podosomes). Therefore, we will look here first at the evidence for mechanical sensing in the cardiovascular system, before comparing the different cytoskeletal arrangements and adhesion sites in cardiomyocytes and vascular smooth muscle cells and what is known about mechanical sensing through the various structures.

show abstract

Hypertensive Pressure Mechanosensing Alone Triggers Lipid Droplet Accumulation and Transdifferentiation of Vascular Smooth Muscle Cells to Foam Cells

Swiatlowska,

Tipping,

Marhuenda

et al. 2023

Advanced Science

Self Cite

View full text Add to dashboard Cite

Arterial Vascular smooth muscle cells (VSMCs) play a central role in the onset and progression of atherosclerosis. Upon exposure to pathological stimuli, they can take on alternative phenotypes that, among others, have been described as macrophage like, or foam cells. VSMC foam cells make up >50% of all arterial foam cells and have been suggested to retain an even higher proportion of the cell stored lipid droplets, further leading to apoptosis, secondary necrosis, and an inflammatory response. However, the mechanism of VSMC foam cell formation is still unclear. Here, it is identified that mechanical stimulation through hypertensive pressure alone is sufficient for the phenotypic switch. Hyperspectral stimulated Raman scattering imaging demonstrates rapid lipid droplet formation and changes to lipid metabolism and changes are confirmed in ABCA1, KLF4, LDLR, and CD68 expression, cell proliferation, and migration. Further, a mechanosignaling route is identified involving Piezo1, phospholipid, and arachidonic acid signaling, as well as epigenetic regulation, whereby CUT&Tag epigenomic analysis confirms changes in the cells (lipid) metabolism and atherosclerotic pathways. Overall, the results show for the first time that VSMC foam cell formation can be triggered by mechanical stimulation alone, suggesting modulation of mechanosignaling can be harnessed as potential therapeutic strategy.

show abstract

Mix and (mis-)match – The mechanosensing machinery in the changing environment of the developing, healthy adult and diseased heart

Cited by 39 publications

References 160 publications

Probing the nanoscale organisation and multivalency of cell surface receptors: DNA origami nanoarrays for cellular studies with single-molecule control

Probing the nanoscale organisation and multivalency of cell surface receptors: DNA origami nanoarrays for cellular studies with single-molecule control

Costameres, dense plaques and podosomes: the cell matrix adhesions in cardiovascular mechanosensing

Hypertensive Pressure Mechanosensing Alone Triggers Lipid Droplet Accumulation and Transdifferentiation of Vascular Smooth Muscle Cells to Foam Cells

Contact Info

Product

Resources

About