Calculation of the force field required for nucleus deformation during cell migration through constrictions.
Calculation of the force field required for nucleus deformation during cell migration through constrictions.
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DOI：
10.1371/journal.pcbi.1008592
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发表时间：
2021-05
影响因子：
4.3
通讯作者：
Hawkins RJ
中科院分区：
文献类型：
--
作者：
Estabrook ID;Thiam HR;Piel M;Hawkins RJ
在封闭的细胞迁移过程中，细胞核必须变形才能使细胞通过小的收缩。这种核变形需要很大的力。变形力场的直接实验测量是极具挑战性的。然而，核形状的实验图像相对容易获得。因此，本文提出了一种基于变形前后核实验图像分析的变形力场预测计算方法。这样的逆计算在技术上是不平凡的，它依赖于原子核的力学模型。在这里，我们比较两个简单的连续体弹性模型的细胞核进行变形。在第一种情况下，我们把原子核看作是一个均匀的弹性固体，在第二种情况下，我们把原子核看作是一个弹性壳层。对于这些模型，我们计算了产生变形所需的力场，这些变形是由树突状细胞核在微通道中迁移的实验图像给出的，这些微通道具有控制尺寸的收缩。这些微通道提供了一个简化的密闭环境，模拟了组织中细胞的经历。我们的计算预测了当一个迁移细胞遇到收缩时，一个变形的细胞核所感受到的力。由于变形力场的直接实验测量是非常具有挑战性的，并且尚未实现，因此我们的数值方法可以做出重要的预测，从而激励进一步的实验，即使所有参数尚未获得。我们展示了我们的方法的力量，通过展示它是如何预测与核周围肌动蛋白聚合相对应的侧向力，为肌动蛋白产生的力在核进入收缩时挤压核的侧面提供了证据。此外，我们开发的算法可以适用于分析其他情况下的变形实验图像。许多类型的细胞能够通过比细胞静止半径更窄的收缩来迁移和挤压。例如，免疫细胞和转移性癌细胞都会改变它们的形状，通过它们移动的复杂组织介质中的小孔进行迁移。在迁移过程中，细胞核比细胞质更难变形，因此细胞通过比细胞核静止大小更小的空间需要很大的力。这些力的实验测量极具挑战性，但在许多实验室中定期获得核变形的实验图像。因此，我们提出了一种计算方法来分析核变形的实验图像，以推断产生这种变形所需的力。原子核的力学模型对于这种分析是必要的，在这里我们提出两个不同的模型。我们的计算工具使我们能够从显微镜图像中获得引起变形的力的详细信息，从而为肌动蛋白产生的力在细胞核进入收缩时挤压细胞核的侧面提供证据。
During cell migration in confinement, the nucleus has to deform for a cell to pass through small constrictions. Such nuclear deformations require significant forces. A direct experimental measure of the deformation force field is extremely challenging. However, experimental images of nuclear shape are relatively easy to obtain. Therefore, here we present a method to calculate predictions of the deformation force field based purely on analysis of experimental images of nuclei before and after deformation. Such an inverse calculation is technically non-trivial and relies on a mechanical model for the nucleus. Here we compare two simple continuum elastic models of a cell nucleus undergoing deformation. In the first, we treat the nucleus as a homogeneous elastic solid and, in the second, as an elastic shell. For each of these models we calculate the force field required to produce the deformation given by experimental images of nuclei in dendritic cells migrating in microchannels with constrictions of controlled dimensions. These microfabricated channels provide a simplified confined environment mimicking that experienced by cells in tissues. Our calculations predict the forces felt by a deforming nucleus as a migrating cell encounters a constriction. Since a direct experimental measure of the deformation force field is very challenging and has not yet been achieved, our numerical approaches can make important predictions motivating further experiments, even though all the parameters are not yet available. We demonstrate the power of our method by showing how it predicts lateral forces corresponding to actin polymerisation around the nucleus, providing evidence for actin generated forces squeezing the sides of the nucleus as it enters a constriction. In addition, the algorithm we have developed could be adapted to analyse experimental images of deformation in other situations. Many cell types are able to migrate and squeeze through constrictions that are narrower than the cell’s resting radius. For example, both immune cells and metastatic cancer cells change their shape to migrate through small holes in the complex tissue media they move in. During migration the cell nucleus is more difficult to deform than the cell cytoplasm and therefore significant forces are required for a cell to pass through spaces that are smaller than the resting size of the nucleus. Experimental measurements of these forces are extremely challenging but experimental images of nuclear deformation are regularly obtained in many labs. Therefore we present a computational method to analyse experimental images of nuclear deformation to deduce the forces required to produce such deformations. A mechanical model of the nucleus is necessary for this analysis and here we present two different models. Our computational tool enables us to obtain detailed information about forces causing deformation from microscopy images and consequently provide evidence for actin generated forces squeezing the sides of the nucleus as it enters a constriction.
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影响因子：
2.8
作者：
Davidson, Patricia M.;Denais, Celine;Bakshi, Maya C.;Lammerding, Jan
通讯作者：
Lammerding, Jan
影响因子：
4.8
作者：
Balzer, Eric M.;Tong, Ziqiu;Konstantopoulos, Konstantinos
通讯作者：
Konstantopoulos, Konstantinos
DOI：
10.1007/978-1-61779-207-6_28
发表时间：
2011-01-01
期刊：
CELL MIGRATION: DEVELOPMENTAL METHODS AND PROTOCOLS, SECOND EDITION
影响因子：
--
作者：
Heuze, Melina L.;Collin, Olivier;Piel, Matthieu
通讯作者：
Piel, Matthieu
影响因子：
64.8
作者：
Laemmermann, Tim;Bader, Bernhard L.;Sixt, Michael
通讯作者：
Sixt, Michael
影响因子：
3.5
作者：
Giverso, C.;Grillo, A.;Preziosi, L.
通讯作者：
Preziosi, L.