Void closure dynamics in the densifying spindle-shaped fibroblast monolayer

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题名:	Void closure dynamics in the densifying spindle-shaped fibroblast monolayer
作者:	張允瑄;Zhang, Yun-Xuan
贡献者:	物理學系
关键词:	細胞;自主性向列結構;細胞運動;集體運動;Cells;Active nematics;Cell migration;Collective dynamics
日期:	2021-07-26
上传时间:	2021-12-07 12:05:58 (UTC+8)
出版者:	國立中央大學
摘要:	單層緻密細胞的集體運動在生物系統中扮演著重要的角色，如胚胎形成、癌細胞轉移、傷口癒合等。主動爬行的細胞可通過細胞間隙 (cell junction) 與鄰近細胞產生交互作用，形成強耦合自主多體系統 (coupled many-body active system)。此外，細胞型態可更進一步影響集體合作運動的狀態。我們研究單層緻密纖維母細胞形成過程中結構及動力行為的演化。單層纖維母細胞形成相互連結的細胞網路後，空洞 (無細胞區) 的大小呈現多重尺度分布。細胞經由細胞分裂及自主爬行運動填滿空間中的空洞以形成單層緻密細胞。在此過程中，長形纖維母細胞與鄰近細胞呈平行排列並形成向列區塊 (nematic domain)。隨著細胞分裂，這些向列區塊與鄰近區塊相遇並在交界處產生非均向排列的區域，導致細胞團簇在邊界上形成不規則的形狀，進而影響空洞的結構與周圍細胞的動力行為以及單層緻密細胞的形成過程。邊界的不規則度隨空洞大小遞增。大尺度的不規則空洞讓突出細胞(protruding cusp tips) 更容易在空洞的邊界形成，並透過自主爬行運動形成橋狀突出至大空洞對邊，將之分裂為小尺度空洞。長形纖維母細胞之型態逐漸隨著細胞密度增加而變短，減少細胞向列之特性，進而准許小尺度空洞周圍的細胞突破拓樸限制 (topological constraint) 並以推擠及細胞換位的方式填滿空洞。因此，單層緻密纖維母細胞的形成將經歷大尺度及小尺度空洞塌縮的兩個不同階段。;Cell monolayer plays a crucial role in many biological processes including embryogenesis, tumorigenesis, and wound healing. It is a model coupled many-body active systems exhibiting collective motions through the interaction between the self-propelling and mutual couplings. Different from cobblestone-like epithelial cells which exhibit isotropic migrating directions, spindle-shaped fibroblasts migrate along their long axis and align with their neighbors, resulting in the formation of nematic domains and topological defects in cell monolayers. While the dynamics and structures of confluent cell monolayer are well studied, the collapsing processes of the cell-free areas (voids) in the densification of fibroblast monolayer before reaching the confluent state remain obscure. In this work, we experimentally investigate the dynamical evolutions of the densifying spindle-shaped fibroblast monolayer before reaching the confluent state. It is found that, after cells form a connected network, voids are spontaneously formed with multiscale sizes, whose boundaries can be classified into convex and cusp-shaped concave boundaries. With increasing time, voids collapse due to the increasing cell density through cell proliferation. For large voids, cells at the cusp shaped concave boundary form extending bridges to split a large void into smaller voids. In smaller voids, the crowding induced by increasing cell density shortens cell lengths. It decreases the nematic cell alignment effect and allows cell topological rearrangements nearby the convex void boundaries, which in turn reduces the number of cells surrounding the void boundary and is the key for the final void closure.
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