Mechanical Fingerprint of Senescence in Endothelial Cells

Chala, Nafsika; Moimas, Silvia; Giampietro, Costanza; Zhang, Xinyu; Zambelli, Tomaso; Exarchos, Vasileios; Nazari-Shafti, Timo Z.; Poulikakos, Dimos; Ferrari, Aldo

doi:10.1021/acs.nanolett.1c00064

Cited by 35 publications

(28 citation statements)

References 63 publications

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“…Senescent endothelial cells fail to change shape in response to flow [ 37 ] and generate monolayers where the cell aspect ratio is unaffected, while the cell orientation remains randomly distributed despite the exposure to WSS ( Figure ). The functional decay of senescent cells was modeled by including particles that do not change shape in response to external fields in the in silico representation, which we term senescent particles.…”

Section: Resultsmentioning

confidence: 99%

“…The biological phenomenon of senescence subtends to the loss of endothelial cell adaptivity to flow. [ 37 ] Individual endothelial cells drift to functional decay, driven by the timely accumulation of genetic and metabolic damage. [ 24 ] This could lead to a progressive impairment of the collective response and functionality in tissues populated by a growing number of senescent cells.…”

Section: Discussionmentioning

confidence: 99%

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Bistability of Dielectrically Anisotropic Nematic Crystals and the Adaptation of Endothelial Collectives to Stress Fields

et al. 2022

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Endothelial monolayers physiologically adapt to flow and flow-induced wall shear stress, attaining ordered configurations in which elongation, orientation, and polarization are coherently organized over many cells. Here, with the flow direction unchanged, a peculiar bi-stable (along the flow direction or perpendicular to it) cell alignment is observed, emerging as a function of the flow intensity alone, while cell polarization is purely instructed by flow directionality. Driven by the experimental findings, the parallelism between endothelia is delineated under a flow field and the transition of dual-frequency nematic liquid crystals under an external oscillatory electric field. The resulting physical model reproduces the two stable configurations and the energy landscape of the corresponding system transitions. In addition, it reveals the existence of a disordered, metastable state emerging upon system perturbation. This intermediate state, experimentally demonstrated in endothelial monolayers, is shown to expose the cellular system to a weakening of cell-to-cell junctions to the detriment of the monolayer integrity. The flow-adaptation of monolayers composed of healthy and senescent endothelia is successfully predicted by the model with adjustable nematic parameters. These results may help to understand the maladaptive response of in vivo endothelial tissues to disturbed hemodynamics and the progressive functional decay of senescent endothelia.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bistability of Dielectrically Anisotropic Nematic Crystals and the Adaptation of Endothelial Collectives to Stress Fields

et al. 2022

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“…All these mechanisms contribute to age-related hypertension. Chala et al, in an in vitro model of endothelial senescence, showed that endothelial cells have a reduced capacity to adapt to the local hemodynamic conditions [ 69 ] functionally. Interestingly, recent experimental studies showed that disturbed flow induces endothelial senescence.…”

Section: Endothelial Dysfunction and Impaired Angiogenesis In The Eld...mentioning

confidence: 99%

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Pacinella

Ciaccio

Tuttolomondo

2022

IJMS

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Vascular diseases of the elderly are a topic of enormous interest in clinical practice, as they have great epidemiological significance and lead to ever-increasing healthcare expenditures. The mechanisms underlying these pathologies have been increasingly characterized over the years. It has emerged that endothelial dysfunction and chronic inflammation play a diriment role among the most relevant pathophysiological mechanisms. As one can easily imagine, various processes occur during aging, and several pathways undergo irreversible alterations that can promote the decline and aberrations that trigger the diseases above. Endothelial dysfunction and aging of circulating and resident cells are the main characteristics of the aged organism; they represent the framework within which an enormous array of molecular abnormalities occur and contribute to accelerating and perpetuating the decline of organs and tissues. Recognizing and detailing each of these dysfunctional pathways is helpful for therapeutic purposes, as it allows one to hypothesize the possibility of tailoring interventions to the damaged mechanism and hypothetically limiting the cascade of events that drive the onset of these diseases. With this paper, we have reviewed the scientific literature, analysing the pathophysiological basis of the vascular diseases of the elderly and pausing to reflect on attempts to interrupt the vicious cycle that connotes the diseases of aging, laying the groundwork for therapeutic reasoning and expanding the field of scientific research by moving from a solid foundation.

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“…As mentioned, previous SCFS techniques did not produce a sufficient data output, and even low-cell-number SCFS studies suggested that the measured SCFS parameters do not follow a specific distribution. Namely, the maximal single-cell adhesion force ( F max ), adhesion energy ( E max ), and the traveled distance of the cantilever, with respect to the surface at F max ( D max ) were typically investigated 7 , 10 , 19 , 21 , 36 . Importantly, low throughput does not allow studying the distributions of large cell populations or revealing possible subpopulations.…”

Section: Introductionmentioning

confidence: 99%

Population distributions of single-cell adhesion parameters during the cell cycle from high-throughput robotic fluidic force microscopy

Nagy

Kanyo

Vörös

et al. 2022

Sci Rep

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Single-cell adhesion plays an essential role in biological and biomedical sciences, but its precise measurement for a large number of cells is still a challenging task. At present, typical force measuring techniques usually offer low throughput, a few cells per day, and therefore are unable to uncover phenomena emerging at the population level. In this work, robotic fluidic force microscopy (FluidFM) was utilized to measure the adhesion parameters of cells in a high-throughput manner to study their population distributions in-depth. The investigated cell type was the genetically engineered HeLa Fucci construct with cell cycle-dependent expression of fluorescent proteins. This feature, combined with the high-throughput measurement made it possible for the first time to characterize the single-cell adhesion distributions at various stages of the cell cycle. It was found that parameters such as single-cell adhesion force and energy follow a lognormal population distribution. Therefore, conclusions based on adhesion data of a low number of cells or treating the population as normally distributed can be misleading. Moreover, we found that the cell area was significantly the smallest, and the area normalized maximal adhesion force was significantly the largest for the colorless cells (the mitotic (M) and early G1 phases). Notably, the parameter characterizing the elongation of the cells until the maximum level of force between the cell and its substratum was also dependent on the cell cycle, which quantity was the smallest for the colorless cells. A novel parameter, named the spring coefficient of the cell, was introduced as the fraction of maximal adhesion force and maximal cell elongation during the mechanical detachment, which was found to be significantly the largest for the colorless cells. Cells in the M phase adhere in atypical way, with so-called reticular adhesions, which are different from canonical focal adhesions. We first revealed that reticular adhesion can exert a higher force per unit area than canonical focal adhesions, and cells in this phase are significantly stiffer. The possible biological consequences of these findings were also discussed, together with the practical relevance of the observed population-level adhesion phenomena.

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Mechanical Fingerprint of Senescence in Endothelial Cells

Cited by 35 publications

References 63 publications

Bistability of Dielectrically Anisotropic Nematic Crystals and the Adaptation of Endothelial Collectives to Stress Fields

Bistability of Dielectrically Anisotropic Nematic Crystals and the Adaptation of Endothelial Collectives to Stress Fields

Endothelial Dysfunction and Chronic Inflammation: The Cornerstones of Vascular Alterations in Age-Related Diseases

Population distributions of single-cell adhesion parameters during the cell cycle from high-throughput robotic fluidic force microscopy

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