Um vislumbre do sentido do tato das células enquanto constroem tecidos durante a embriogênese
Construir tecidos e órgãos é uma das tarefas mais complexas e essenciais que as células devem realizar durante a embriogênese. Nessa tarefa coletiva, as células se comunicam por meio de uma variedade de métodos de comunicação, incluindo sinais...
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)
O comprimento da junção estabelece o início da plasticidade do tecido. a, Esboço mostrando uma visão lateral de um embrião em estágio de dez somitos destacando a região posterior do corpo (retângulo preto pontilhado) onde os progenitores mesodérmicos se diferenciam progressivamente à medida que transitam do MPZ para o PSM (i). Seções confocais ao longo do plano sagital de tecidos que se estendem posteriormente em embriões Tg(actb2:MA-Citrine) marcados com membrana (invertidos) contendo gotículas de ferrofluido (ciano) em diferentes regiões ao longo do eixo AP, ou seja, o A-PSM, o PSM posterior ( P-PSM) e o MPZ (ii). V, ventral; D, dorsal; A, anterior; P, posterior. Os contornos tracejados vermelhos destacam cada região (A-PSM, P-PSM e MPZ). b, Seção confocal da gota (ciano) durante a atuação (campo magnético LIGADO; etiqueta da membrana, invertida; i). A linha tracejada vermelha indica o contorno da gota e as setas indicam a direção das forças aplicadas pela gota. Esboços definindo o alongamento induzido da gota e ao longo da direção do campo magnético aplicado HH e o pré-alongamento da gota antes da atuação, e0 (ii). As linhas tracejadas indicam a gota não alongada. c, Valores médios (pontos) e medianos (linhas) do tamanho da célula (diâmetro, d; cinza) e comprimento juncional (?; vermelho) no MPZ e PSM, reanalisados ??a partir da literatura. A inserção à direita mostra os parâmetros. Barras de erro, sem d, Exemplos da evolução temporal da deformação da gota (extensão normalizada da gota, e/d¯, onde d¯ é o tamanho médio da célula (diâmetro); tensão induzida) durante os ciclos de atuação (OFF–ON–OFF) para valores diferentes do campo magnético aplicado, levando a valores variáveis ??de e M. Ambos e 0 e e R são definidos na inserção. e,f, Alongamento residual da gota normalizado pelo tamanho médio da célula, (e R ?e 0)/d¯(e) ou por comprimento juncional médio, (e R ?e 0 )/?¯ (f), para valores variados do alongamento máximo de gota aplicado (e M ?? e 0 ) normalizado pelo tamanho médio da célula (e ) ou comprimento juncional (f) no mesoderma paraxial posterior. As linhas vermelhas verticais em e e f indicam o início da deformação plástica irreversível. A mediana e o intervalo interquartílico são mostrados. Os valores de P foram obtidos a partir de testes t bicaudais de uma amostra. NS, não significativo; **P = 0,0025, ****P < 0,0001. g, Instantâneos mostrando seções confocais de tecido próximo a uma gota (linha vermelha pontilhada) durante um ciclo de atuação (OFF–ON–OFF) causando transições T1 que levam a mudanças plásticas na arquitetura local do tecido (abaixo). Crédito: Nature Materials(2022). DOI: 10.1038/s41563-022-01433-9
Construir tecidos e órgãos é uma das tarefas mais complexas e essenciais que as células devem realizar durante a embriogênese. Nessa tarefa coletiva, as células se comunicam por meio de uma variedade de métodos de comunicação, incluindo sinais bioquímicos — semelhantes ao olfato de uma célula — e pistas mecânicas — o sentido do tato da célula.
Pesquisadores em uma variedade de disciplinas são fascinados pela comunicação celular há décadas. O professor Otger Campàs, juntamente com seus colegas do Cluster de Excelência em Física da Vida (PoL) da Technische Universität Dresden e da Universidade da Califórnia em Santa Bárbara (UCSB), agora conseguiram desvendar outro mistério em torno da questão de como as células usam seus sentidos do toque para tomar decisões vitais durante a embriogênese. Seu artigo foi publicado na revista Nature Materials.
Testando os arredores
Em seu artigo, os pesquisadores relatam como as células dentro de um embrião vivo testam mecanicamente seu ambiente e quais parâmetros e estruturas mecânicas eles percebem. "Sabemos muito sobre como as células percebem e respondem a sinais mecânicos em um prato. No entanto, seu microambiente é bastante diferente dentro de um embrião e não sabíamos quais sinais mecânicos eles percebem em um tecido vivo ", diz Campàs, presidente do Tissue Diretor Geral de Dinâmica e PoL.
As curas mecânicas ajudam as células a tomar decisões importantes , como dividir, mover ou mesmo diferenciar, processo de diferenciação pelo qual as células-tronco se transformam em células mais especializadas e capazes de desempenhar funções específicas.
Pesquisas anteriores revelaram que as células-tronco colocadas em um substrato sintético dependem fortemente de pistas mecânicas para tomar decisões: células em superfícies com rigidez semelhante a ossos se tornaram osteoblastos (células ósseas), enquanto células em superfícies com rigidez semelhante ao tecido cerebral se tornaram neurônios. As descobertas avançaram muito no campo da engenharia de tecidos, pois os pesquisadores usaram essas dicas mecânicas para criar andaimes sintéticos para persuadir as células-tronco a se desenvolverem nos resultados desejados. Esses andaimes são usados ??hoje em uma variedade de aplicações biomédicas.
Do prato ao embrião vivo
No entanto, um prato não é o habitat natural da célula. Ao construir um organismo, as células não estão em contato com andaimes sintéticos em um prato plano, mas sim com materiais vivos complexos em três dimensões.
Na última década, o grupo de pesquisa do Prof. Campàs descobriu as pistas mecânicas que orientam as células nos tecidos complexos de um embrião. Usando uma técnica única desenvolvida em seu laboratório , os pesquisadores puderam sondar o tecido vivo de maneira semelhante às células e descobrir quais estruturas mecânicas as células detectam.
“Primeiro estudamos como as células testam mecanicamente seu microambiente à medida que se diferenciam e constroem o eixo do corpo de um vertebrado, à medida que se diferenciam”, diz Campàs. "Células usavam saliências diferentes para empurrar e puxar seu ambiente. Então, quantificamos o quão rápido e forte eles estavam empurrando."
Usando uma gota de óleo ferromagnético que eles inseriram entre as células em desenvolvimento e sujeitando-a a um campo magnético controlado, eles conseguiram imitar essas minúsculas forças e medir a resposta mecânica das células ao redor.
Sentindo a arquitetura do tecido e as células mudam o destino
Crítico para as ações dessas células embrionárias é seu estado físico coletivo, que Campàs e seu grupo de pesquisa descreveram em um artigo anterior como o de uma espuma ativa, semelhante em consistência a espuma de sabão ou espuma de cerveja, com células agrupadas por adesão celular e puxando um ao outro.
O que as células estão sondando mecanicamente, Campàs e sua equipe descobriram, é o estado coletivo dessa "espuma viva" - quão rígida ela é e quão confinada é a assembleia. "E bem no momento em que as células se diferenciam e decidem mudar seu destino, há uma mudança nas propriedades materiais do tecido que elas percebem." Segundo ele, no momento em que as células dentro do tecido decidem seu destino, o tecido cai em rigidez.
Daqui para frente
O que ainda não foi comprovado neste estudo é a complexa questão de saber se – e se sim, como – a mudança na rigidez no ambiente embrionário impulsiona a mudança no estado celular.
"Existe uma interação entre as características mecânicas das estruturas que as células constroem coletivamente, como tecidos ou órgãos, e as decisões que elas tomam individualmente, pois dependem das sugestões mecânicas que as células percebem no tecido. Essa interação está no cerne de como a natureza constrói os organismos", diz Campàs.
As descobertas deste estudo também podem ter implicações importantes para a engenharia de tecidos. Materiais potenciais que imitam as características de espuma do tecido embrionário, em oposição aos polímeros sintéticos amplamente utilizados ou andaimes de gel, podem permitir que os pesquisadores criem tecidos, órgãos e implantes sintéticos mais robustos e sofisticados no laboratório, com as geometrias e características mecânicas para as funções desejadas.
Mais informações: Alessandro Mongera et al, Mecânica do microambiente celular sondado por células in vivo durante a diferenciação do mesoderma pré-somítico do peixe-zebra, Nature Materials (2022). DOI: 10.1038/s41563-022-01433-9
Informações do periódico: Nature Materials