Emergent collective organization of bone cells in complex curvature fields.

Emergent collective organization of bone cells in complex curvature fields.
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DOI:
10.1038/s41467-023-36436-w
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发表时间:
2023-03-03
影响因子:
16.6
通讯作者:
Zadpoor, Amir A.
Zadpoor, Amir A.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Callens, Sebastien J. P.;Fan, Daniel;van Hengel, Ingmar A. J.;Minneboo, Michelle;Diaz-Payno, Pedro J.;Stevens, Molly M.;Fratila-Apachitei, Lidy E.;Zadpoor, Amir A.

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单个细胞和多细胞系统响应其环境中的细胞尺度曲率,引导迁移,定向和组织形成。然而,在很大程度上仍然不清楚细胞如何共同探索和图案复杂的景观与曲率梯度在欧几里得和非欧几里得光谱。在这里,我们表明,数学设计的基板与控制曲率变化诱导多细胞时空组织的前成骨细胞。我们量化曲率诱导的图案,并发现细胞一般喜欢至少有一个负主曲率的区域。然而,我们也表明,发展中的组织最终可以覆盖不利的弯曲领土,可以桥接基板的大部分,并往往是其特征在于集体对齐的应力纤维。我们证明,这是部分调节细胞收缩性和细胞外基质的发展,强调曲率指导的机械性质。我们的研究结果提供了一个几何角度的细胞与环境的相互作用,可以利用在组织工程和再生医学应用。目前尚不清楚细胞如何在中尺度上对复杂的细胞外几何形状作出反应。在这里,作者研究了不同曲率景观中骨细胞的组织,观察到局部凹陷,多细胞桥接和集体应力纤维取向的偏好。
Individual cells and multicellular systems respond to cell-scale curvatures in their environments, guiding migration, orientation, and tissue formation. However, it remains largely unclear how cells collectively explore and pattern complex landscapes with curvature gradients across the Euclidean and non-Euclidean spectra. Here, we show that mathematically designed substrates with controlled curvature variations induce multicellular spatiotemporal organization of preosteoblasts. We quantify curvature-induced patterning and find that cells generally prefer regions with at least one negative principal curvature. However, we also show that the developing tissue can eventually cover unfavorably curved territories, can bridge large portions of the substrates, and is often characterized by collectively aligned stress fibers. We demonstrate that this is partly regulated by cellular contractility and extracellular matrix development, underscoring the mechanical nature of curvature guidance. Our findings offer a geometric perspective on cell-environment interactions that could be harnessed in tissue engineering and regenerative medicine applications. It remains unclear how cells respond to complex extracellular geometries at the mesoscale. Here, the authors study the organization of bone cells in landscapes with varying curvatures, observing a preference for local concavities, multicellular bridging, and collective stress fiber orientation.
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