The basement membrane as a structured surface – role in vascular health and disease

Leclech, Claire; Natale, Carlo F.; Barakat, Abdul I.

doi:10.1242/jcs.239889

Cited by 68 publications

(65 citation statements)

References 127 publications

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“…Interestingly, the range of dimensionalities of these nanotopographies closely resemble e.g. those found in different basement membranes 16 .…”

Section: Resultssupporting

confidence: 68%

“…The surface morphology of the cluster-assembled zirconia films are characterised by distinct peaks and valleys (Fig. 1A), defining a complex random pattern of nanometric features, whose dimensions and spatial distribution resemble those found in natural ECM topographies (in particular in basement membranes) 3,7,14,15,16,37 . Various cell/probe contact times covering different stages of the critical window of nascent adhesion formation towards maturation to focal adhesions 38,39 , i.e.…”

Section: Resultsmentioning

confidence: 99%

“…The configuration of topographical nano-3D features determines spatial parameters relevant for mechanosensing, such as adhesion site areas and spacing, and is therefore capable of modulating IAC formation and signalling 6,7,8,9,10,11,12,13 . Moreover, the three-dimensionality of the surface topography introduces also further levels of complexity, compared to flat substrates 3,7,14,15,16 (Fig. 1A).…”

Section: Introductionmentioning

confidence: 99%

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The glycocalyx affects the mechanotransductive perception of the topographical microenvironment

Chighizola

Dini

Marcotti

et al. 2021

Preprint

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The cell/microenvironment interface is the starting point of integrin-mediated mechanotransduction, but many details of mechanotransductive signal integration remain elusive due to the complexity of the involved (extra)cellular structures, such as the glycocalyx. We used engineered nano-bio interfaces with extracellular matrix nanotopography-mimicking features to analyse the impact of the glycocalyx on nano-mechanosensing. Our data demonstrates that the glycocalyx configuration affects spatiotemporal nanotopography-sensitive mechanotransductive events at the cell/microenvironment interface. Opposing effects of glycocalyx removal were observed, when comparing flat and specific nanotopographical conditions (i.e., 15 nm root-mean-square (rms) roughness). In fact, the excessive force loading and retrograde actin flow speed, characteristic for the 15 nm rms nanotopography in the presence of native glycocalyx, are strongly reduced in its absence. Conversely, on the flat substrate, these parameters increased upon glycocalyx-targeting enzymatic treatment. Our results highlight the importance of the glycocalyx configuration in a molecular clutch force loading-dependent cellular mechanism for nano-mechanosensing of the topography.

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“…Interestingly, the range of dimensionalities of these nanotopographies closely resemble e.g. those found in different basement membranes 16 .…”

Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The glycocalyx affects the mechanotransductive perception of the topographical microenvironment

Chighizola

Dini

Marcotti

et al. 2021

Preprint

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“…Physical anchoring to the BM Pericytes interact physically with both the BM and neighboring ECs, as well as with other pericytes. The microvascular BM is formed by two ECM networks, one comprising laminin and the other collagen IV, bound together by perlecan (HSPG2) and nidogen (NID1 and NID2) (Leclech et al, 2020;Thomsen et al, 2017). In addition, fibronectin patches, in either circumferential crescent shapes or dots, punctuate the BM and are found exclusively between pericytes and ECs (Courtoy and Boyles, 1983).…”

Section: Pericyte Physical Interactionsmentioning

confidence: 99%

Pericyte mechanics and mechanobiology

Dessalles

Babataheri

Barakat

2021

Journal of Cell Science

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Pericytes are mural cells of the microvasculature, recognized by their thin processes and protruding cell body. Pericytes wrap around endothelial cells and play a central role in regulating various endothelial functions, including angiogenesis and inflammation. They also serve as a vascular support and regulate blood flow by contraction. Prior reviews have examined pericyte biological functions and biochemical signaling pathways. In this Review, we focus on the role of mechanics and mechanobiology in regulating pericyte function. After an overview of the morphology and structure of pericytes, we describe their interactions with both the basement membrane and endothelial cells. We then turn our attention to biophysical considerations, and describe contractile forces generated by pericytes, mechanical forces exerted on pericytes, and pericyte responses to these forces. Finally, we discuss 2D and 3D engineered in vitro models for studying pericyte mechano-responsiveness and underscore the need for more evolved models that provide improved understanding of pericyte function and dysfunction.

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“…During inflammation, immune cells squeeze in between endothelial cells or through them before transmigrating through the basement membrane. The penetration of cells into the tissues, called diapedesis, might be modified by a reorganization of the basement membrane that can lead to diseases (Friedl and Weigelin 2008;Korpos et al 2013;Leclech et al 2020). 1D scenarios are less common physiologically but still present in vivo.…”

Section: Challenges and Scenarios Immune Cells Encounter In Vivomentioning

confidence: 99%

Characterization of immune cell migration using microfabrication

Vesperini

Montalvo

et al. 2021

Biophys Rev

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The immune system provides our defense against pathogens and aberrant cells, including tumorigenic and infected cells. Motility is one of the fundamental characteristics that enable immune cells to find invading pathogens, control tissue damage, and eliminate primary developing tumors, even in the absence of external treatments. These processes are termed “immune surveillance.” Migration disorders of immune cells are related to autoimmune diseases, chronic inflammation, and tumor evasion. It is therefore essential to characterize immune cell motility in different physiologically and pathologically relevant scenarios to understand the regulatory mechanisms of functionality of immune responses. This review is focused on immune cell migration, to define the underlying mechanisms and the corresponding investigative approaches. We highlight the challenges that immune cells encounter in vivo, and the microfabrication methods to mimic particular aspects of their microenvironment. We discuss the advantages and disadvantages of the proposed tools, and provide information on how to access them. Furthermore, we summarize the directional cues that regulate individual immune cell migration, and discuss the behavior of immune cells in a complex environment composed of multiple directional cues.

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The basement membrane as a structured surface – role in vascular health and disease

Cited by 68 publications

References 127 publications

The glycocalyx affects the mechanotransductive perception of the topographical microenvironment

The glycocalyx affects the mechanotransductive perception of the topographical microenvironment

Pericyte mechanics and mechanobiology

Characterization of immune cell migration using microfabrication

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