The initial step of a number of human or plant fungal infections requires active penetration of host tissue. For example, active penetration of intestinal epithelia by Candida albicans is critical for dissemination from the gut into the bloodstream. However, little is known about how this fungal pathogen copes with resistive forces upon host cell invasion. In the present study, we have used PDMS micro-fabrication to probe the ability of filamentous C. albicans cells to penetrate and grow invasively in substrates of different stiffness. We show that there is a threshold for penetration that corresponds to a stiffness of ~ 200 kPa and that invasive growth within a stiff substrate is characterized by dramatic filament buckling, along with a stiffness-dependent decrease in extension rate. We observed a striking alteration in cell morphology, i.e., reduced cell compartment length and increased diameter during invasive growth, that is not due to depolarization of active Cdc42, but rather occurs at a substantial distance from the site of growth as a result of mechanical compression. Our data reveal that in response to this compression, active Cdc42 levels are increased at the apex, whereas active Rho1 becomes depolarized, similar to that observed in membrane protrusions. Our results show that cell growth and morphology are altered during invasive growth, suggesting stiffness dictates the host cells that C. albicans can penetrate.

中文翻译：

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机械力诱导人类真菌病原体的形态变化。

许多人或植物真菌感染的起始步骤都需要主动渗透宿主组织。例如，白色念珠菌对肠道上皮的积极渗透对于从肠内扩散到血液中至关重要。然而，对于这种真菌病原体如何抵抗宿主细胞入侵时的抵抗力知之甚少。在本研究中，我们已使用PDMS微细加工来探测丝状白色念珠菌细胞在不同硬度的基质中穿透和侵袭性生长的能力。我们显示，存在一个对应于〜200 kPa刚度的穿透阈值，并且在坚硬基材内的侵入性生长的特征是细丝屈曲，以及刚度相关的延伸速率下降。我们观察到细胞形态发生了惊人的变化，即 侵入性生长过程中细胞室长度的减小和直径的增加，这不是由于活性Cdc42的去极化引起的，而是由于机械压缩而在距生长部位很远的距离处发生的。我们的数据显示，响应此压缩，活动的Cdc42水平在顶点处增​​加，而活动的Rho1变得去极化，类似于在膜突起中观察到的。我们的结果表明，在侵袭性生长过程中，细胞的生长和形态发生了变化，这表明刚度决定了白色念珠菌可以穿透的宿主细胞。我们的数据显示，响应此压缩，活动的Cdc42水平在顶点处增​​加，而活动的Rho1变得去极化，类似于在膜突起中观察到的。我们的结果表明，在侵袭性生长过程中，细胞的生长和形态发生了变化，这表明刚度决定了白色念珠菌可以穿透的宿主细胞。我们的数据显示，响应此压缩，活动的Cdc42水平在顶点处增​​加，而活动的Rho1变得去极化，类似于在膜突起中观察到的。我们的结果表明，在侵袭性生长过程中，细胞的生长和形态发生了变化，这表明刚度决定了白色念珠菌可以穿透的宿主细胞。