Unveiling mechanotransduction during collective cell migration

Collective cell migration (CCM) describes the coordinated movement and behavior of a group of cells. It relies heavily on cell-cell communication and microenvironmental interactions and is essential for embryonic morphogenesis, angiogenesis, wound repair and cancer invasion. CCM depends on physical forces applied directly onto adherent junctions (AJs). AJs are composed by a dynamic protein complex including core members of the cadherin and catenin families, and additional partners such as vinculin and actin regulators. Efficient mechanotransduction and collective polarization in CCM is directly dependent on the intricate connectivity between junctional proteins and the actin cytoskeleton. Although α-catenin is essential in cadherin-dependent mechanobiology, it remains unclear whether there are also α-catenin cadherin-independent functions in CCM. Moreover, despite the firm link between actin polymerization and mechanotransduction in CCM, little is known on the mechanisms recruiting and activating the Arp2/3 complex at AJs during CCM. In our lab, we established a method to evaluate cell coordination during CCM using front-rear polarity axis of groups of endothelial cells (ECs). We used this methodology to investigate α-catenin cadherin-independent functions and the mechanisms recruiting Arp2/3 complex at AJs in ECs undergoing CCM. We found that the role of α-catenin in CCM depends primarily on its binding to the cadherin complex, suggesting that cadherin-independent functions of α-catenin is absent in ECs. Additionally, we confirmed that Arp2/3 complex is essential for CCM and collective axial polarity. Mechanistically, we present initial evidences that Arp2/3 complex is recruited specifically to AJs by vinculin. Altogether, our work shows that cadherin-dependent mechanotransduction relies on Arp2/3 complex activity and highlights its function as novel regulator of axial polarity in ECs. Future insights on mechanobiology could provide new clues to design therapies to prevent cancer invasion

The Forces behind Directed Cell Migration

Directed cell migration is an essential building block of life, present when an embryo develops, a dendritic cell migrates toward a lymphatic vessel, or a fibrotic organ fails to restore its normal parenchyma. Directed cell migration is often guided by spatial gradients in a physicochemical property of the cell microenvironment, such as a gradient in chemical factors dissolved in the medium or a gradient in the mechanical properties of the substrate. Single cells and tissues sense these gradients, establish a back-to-front polarity, and coordinate the migration machinery accordingly. Central to these steps we find physical forces. In some cases, these forces are integrated into the gradient sensing mechanism. Other times, they transmit information through cells and tissues to coordinate a collective response. At any time, they participate in the cellular migratory system. In this review, we explore the role of physical forces in gradient sensing, polarization, and coordinating movement from single cells to multicellular collectives. We use the framework proposed by the molecular clutch model and explore to what extent asymmetries in the different elements of the clutch can lead to directional migration

Non-canonical Wnt signaling regulates junctional mechanocoupling during angiogenic collective cell migration

© 2019, Carvalho et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.Morphogenesis of hierarchical vascular networks depends on the integration of multiple biomechanical signals by endothelial cells, the cells lining the interior of blood vessels. Expansion of vascular networks arises through sprouting angiogenesis, a process involving extensive cell rearrangements and collective cell migration. Yet, the mechanisms controlling angiogenic collective behavior remain poorly understood. Here, we show this collective cell behavior is regulated by non-canonical Wnt signaling. We identify that Wnt5a specifically activates Cdc42 at cell junctions downstream of ROR2 to reinforce coupling between adherens junctions and the actin cytoskeleton. We show that Wnt5a signaling stabilizes vinculin binding to alpha-catenin, and abrogation of vinculin in vivo and in vitro leads to uncoordinated polarity and deficient sprouting angiogenesis in Mus musculus. Our findings highlight how non-canonical Wnt signaling coordinates collective cell behavior during vascular morphogenesis by fine-tuning junctional mechanocoupling between endothelial cells.Research was supported by European Research Council starting grant (679368), the H2020-Twinning grant (692322), the Fundação para a Ciência e a Tecnologia funding (grants: IF/00412/2012; EXPL-BEX-BCM-2258–2013; PRECISE-LISBOA-01–0145-FEDER-016394; UID/BIM/50005/2019, a project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência,Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado; and a grant from the Fondation Leducq (17CVD03); and personal fellowships: BD/52224/2013​​ to JRC, BD/105856/2014 to PB, and BD/128375/2017 to CF) and LISBOA-01–0145-FEDER-007391, project cofunded by FEDER, through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, PORTUGAL 2020, and Fundação para a Ciência e a Tecnologia.info:eu-repo/semantics/publishedVersio

Competition for endothelial cell polarity drives vascular morphogenesis in the mouse retina

© 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Blood-vessel formation generates unique vascular patterns in each individual. The principles governing the apparent stochasticity of this process remain to be elucidated. Using mathematical methods, we find that the transition between two fundamental vascular morphogenetic programs-sprouting angiogenesis and vascular remodeling-is established by a shift of collective front-to-rear polarity of endothelial cells in the mouse retina. We demonstrate that the competition between biochemical (VEGFA) and mechanical (blood-flow-induced shear stress) cues controls this collective polarity shift. Shear stress increases tension at focal adhesions overriding VEGFA-driven collective polarization, which relies on tension at adherens junctions. We propose that vascular morphogenetic cues compete to regulate individual cell polarity and migration through tension shifts that translates into tissue-level emergent behaviors, ultimately leading to uniquely organized vascular patterns.Funding: European Research Council: C.A.F. (679368); X.T. (883739). European Commission: C.A.F. and M.O.B. (801423); X.T. and P.R.-C. (731957). H2020-MSCA-PF grants to M.G.-G. (797621) and M.O. (842498). Fondation LeDucq: C.A.F., A.E., and M.O.B. (17CVD03). EPSRC: M.O.B. (EP/T008806/1; EP/R029598/1). Fundação para a Ciência e Tecnologia: C.A.F. (PTDC/MED-PAT/31639/2017; PTDC/BIA-CEL/32180/2017; CEECIND/04251/2017). Spanish Ministry of Science and Innovation: P.R.-C. (PID2019-110298GB-I00); X.T. (PGC2018-099645-B-I00). Generalitat de Catalunya: X.T. and P.R.-C. (2017-SGR-1602). La Caixa Foundation: X.T. and P.R.-C. (LCF/PR/HR20/52400004). Fundació la Marató de TV3: X.T. (201903-30-31-32). EMBO: L.M.F. (ALTF 2-2018)info:eu-repo/semantics/publishedVersio

Grupo de estudos de enfermagem em lesões cutâneas: perspectivas e vivências na graduação / Group of nursing studies in cuts lesions: perspectives and experiences in graduation

Introduction: It is essential for Nursing to value scientific production for the development of an evidence-based practice. The research group is configured as a favorable space for the construction, improvement and development of intellectual skills. Objective: To report the experience of nursing students in founding a study group in the area of injuries. Methodology: Descriptive study of the experience report type about the experience in a group of nursing studies on skin lesions. Results: It was the first group of studies in the Nursing course of the aforementioned institution of higher education, focusing on undergraduate students. Social media were used to publicize the study group, which expanded the scope of the scientific content generated, in addition to exchanging experience with other professionals. The contents discussed in the group meetings were previously thought by the founding members and guiding professors. Active methodologies made it possible for academics to discover new skills, in addition to making them the center of learning Conclusion: The involvement of the academic in the study group allows and facilitates the advancement of knowledge production, which values nursing and allows to go beyond the execution of the technique and allows the action of a reflective practice.

EL ESPECTRO AUTISTA Y LA ADAPTACIÓN DE LOS DERECHOS HUMANOS

Este trabajo pretende abordar la importancia de relativizar el principio de igualdad para las personas con TEA, a través de un análisis profundo de dicho principio y su concepto ante el Sistema Interamericano de Derechos Humanos. Además de señalar las diferencias más latentes entre la igualdad material y formal y repasar casos prácticos con el fin de arrojar luz sobre las razones por las que debe relativizarse el principio en debate. Pretendiendo, con todo lo anterior, demostrar que la relativización del principio constitucional de igualdad es fundamental para garantizar a este grupo específico el acceso a derechos y beneficios que sean capaces de compensar las dificultades que enfrenta por su condición. Haciéndose uso del método de investigación deductivo, utilizando investigaciones científicas, análisis de casos del Sistema Interamericano de Derechos Humanos y doctrinas

Risco de COVID-19 em profissionais de saúde da linha de frente e intervenções: revisão sistemática

Objective: to identify the evidence related to the risks of SARS-CoV-2 exposure in healthcare workers and the interventions adopted. Method: systematic literature review in eight scientific databases and three gray literature repositories. Results: 26 studies identified as risk factors: scarcity, inadequate use or reuse of personal equipment; low adherence to precautionary measures; working in intensive care and COVID-19 sectors; long stay in a closed work environment; sharing eating areas without the use of masks and distance; low knowledge and unpreparedness for disease management. 12 studies identified as interventions: health surveillance programs with early detection, diagnosis and early withdrawal; organization of care flows; double triage; telemedicine; limitation of visits; creation of exclusive sectors for care to COVID-19; qualification and training with virtual tools and simulation. Conclusion: besides the risk of infection, individual, psychosocial and organizational factors made the healthcare work environment unsafe. Interventions should be adopted to mitigate the risks and decrease the professionals' morbidity and mortality.Objetivo: identificar as evidências relacionadas aos riscos de exposição ao SARS-CoV-2 em profissionais de saúde e as intervenções adotadas. Método: revisão sistemática de literatura em oito bases de dados científicas e três repositórios de literatura cinzenta. Resultados: 26 estudos identificaram como fator de risco: escassez, uso inadequado ou reuso de equipamentos individuais; baixa adesão às medidas de precaução; atuação em terapia intensiva e setores COVID-19; longa permanência em ambiente de trabalho fechado; compartilhamento de espaços para alimentação sem uso de máscara e distanciamento; baixo conhecimento e despreparo para atendimento à doença. 12 estudos identificaram como intervenções:  programas de vigilância em saúde com detecção precoce, diagnóstico e afastamento precoce; organização de fluxos de atendimento; triagem dupla; telemedicina; limitação de visitas; criação de setores exclusivos para atendimento à COVID-19; capacitações e treinamentos com ferramentas virtuais e simulação. Conclusão: além do risco de infecção, fatores individuais, psicossociais e organizacionais tornaram o ambiente de trabalho em saúde inseguro. Intervenções devem ser adotadas para mitigar os riscos e diminuir a morbimortalidade dos profissionais

The Molecular Mechanism of Polyphenols in the Regulation of Ageing Hallmarks

Ageing is a complex process characterized mainly by a decline in the function of cells, tissues, and organs, resulting in an increased risk of mortality. This process involves several changes, described as hallmarks of ageing, which include genomic instability, telomere attrition, epigenetic changes, loss of proteostasis, dysregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell depletion, and altered intracellular communication. The determining role that environmental factors such as diet and lifestyle play on health, life expectancy, and susceptibility to diseases, including cancer and neurodegenerative diseases, is wellestablished. In view of the growing interest in the beneficial effects of phytochemicals in the prevention of chronic diseases, several studies have been conducted, and they strongly suggest that the intake of dietary polyphenols may bring numerous benefits due to their antioxidant and anti-inflammatory properties, and their intake has been associated with impaired ageing in humans. Polyphenol intake has been shown to be effective in ameliorating several age-related phenotypes, including oxidative stress, inflammatory processes, impaired proteostasis, and cellular senescence, among other features, which contribute to an increased risk of ageing-associated diseases. This review aims to address, in a general way, the main findings described in the literature about the benefits of polyphenols in each of the hallmarks of ageing, as well as the main regulatory mechanisms responsible for the observed antiageing effects

Effect of Polyphenols Intake on Obesity-Induced Maternal Programming

Excess caloric intake and body fat accumulation lead to obesity, a complex chronic disease that represents a significant public health problem due to the health-related risk factors. There is growing evidence showing that maternal obesity can program the offspring, which influences neonatal phenotype and predispose offspring to metabolic disorders such as obesity. This increased risk may also be epigenetically transmitted across generations. Thus, there is an imperative need to find effective reprogramming approaches in order to resume normal fetal development. Polyphenols are bioactive compounds found in vegetables and fruits that exert its anti-obesity effect through its powerful anti-oxidant and anti-inflammatory activities. Polyphenol supplementation has been proven to counteract the prejudicial effects of maternal obesity programming on progeny. Indeed, some polyphenols can cross the placenta and protect the fetal predisposition against obesity. The present review summarizes the effects of dietary polyphenols on obesity-induced maternal reprogramming as an offspring anti-obesity approach

Stiffness-dependent active wetting enables optimal collective cell durotaxis

The directed migration of cellular clusters enables morphogenesis, wound healing and collective cancer invasion. Gradients of substrate stiffness direct the migration of cellular clusters in a process called collective durotaxis, but the underlying mechanisms remain unclear. Here we unveil a connection between collective durotaxis and the wetting properties of cellular clusters. We show that clusters of cancer cells dewet soft substrates and wet stiff ones. At intermediate stiffness—at the crossover from low to high wettability—clusters on uniform-stiffness substrates become maximally motile, and clusters on stiffness gradients exhibit optimal durotaxis. Durotactic velocity increases with cluster size, stiffness gradient and actomyosin activity. We demonstrate this behaviour on substrates coated with the cell–cell adhesion protein E-cadherin and then establish its generality on substrates coated with extracellular matrix. We develop an active wetting model that explains collective durotaxis in terms of a balance between in-plane active traction and tissue contractility and out-of-plane surface tension. Finally, we show that the distribution of cluster displacements has a heavy tail, with infrequent but large cellular hops that contribute to durotactic migration. Our study demonstrates a physical mechanism of collective durotaxis, through both cell–cell and cell–substrate adhesion ligands, based on the wetting properties of active droplets