Motile Dendritic Cells Sense and Respond to Substrate Geometry.
Motile Dendritic Cells Sense and Respond to Substrate Geometry.
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DOI：
10.1007/s10439-018-2041-7
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发表时间：
2018-09
影响因子：
3.8
通讯作者：
Hammer DA
中科院分区：
文献类型：
--
作者：
Bendell AC;Anderson N;Blumenthal D;Williamson EK;Chen CS;Burkhardt JK;Hammer DA
树突状细胞（DC）迁移是有效呈递抗原给T细胞和启动适应性免疫应答所必需的。尽管其重要性，DC迁移的许多方面还没有被表征。DC遇到具有不同刚度和几何形状的各种环境，但这些参数对DC迁移的影响尚未确定。我们通过比较标准迁移表面（聚二甲基硅氧烷（PDMS）涂层盖玻片）和微柱阵列检测器（mPAD）上的DC运动性来解决这个问题。这两个表面在刚度和几何形状上都不同。我们发现，DC迁移受基板类型的影响，与旋转涂布的PDMS盖玻片相比，由PDMS制成的mPAD上的速度显着增加，持续时间显着减少。为了确定柱阵列的几何形状或顺应性是否是DC迁移中这些变化的原因，我们在相同几何形状但不同刚度的mPAD上定量DC运动性。在这些mPAD上，迁移是不可区分的，这表明DC对配体呈递的几何形状而不是刚度有响应。此外，通过以与mPAD阵列相似的几何形状在平坦PDMS表面上微图案化配体，我们确定DC响应于印刷配体的几何形状。最后，我们使用了各种小分子抑制剂，以确定参与几何传感的途径。我们看到肌球蛋白收缩性和α5β1整合素参与的重要作用。我们还注意到，当树突状细胞在柱子上活动时，肌动蛋白细胞骨架显著重组为动态肌动蛋白环。从这些实验中，我们得出结论，DCs是不敏感的底物顺应性的范围内测试，但响应几何形状的变化，通过一种机制，涉及整合素功能，肌球蛋白收缩性，和肌动蛋白细胞骨架的重塑。作为一种可能的解释，我们假设一个一致的作用，丝状伪足的延伸和收缩的驱动程序的DC运动。
Dendritic cell (DC) migration is required for efficient presentation of antigen to T cells and the initiation of an adaptive immune response. In spite of its importance, many aspects of DC migration have not been characterized. DCs encounter a variety of environments with different stiffness and geometry, but the effect of these parameters on DC migration has not yet been determined. We addressed this question by comparing DC motility on standard migration surfaces (polydimethylsiloxane (PDMS)-coated coverslips) and micropost array detectors (mPADs). These two surfaces differ in both stiffness and geometry. We found that DC migration was affected by substrate type, with significant increases in speed and significant decreases in persistence time on mPADs made of PDMS as compared to spin-coated PDMS coverslips. To determine whether the geometry or compliance of the post arrays was responsible for these changes in DC migration, we quantified DC motility on mPADs of identical geometry but different stiffness. Migration was indistinguishable on these mPADs, suggesting that DCs are responsive to geometry of ligand presentation and not stiffness. Further, by micropatterning ligands on flat PDMS surfaces in similar geometries to the mPAD arrays, we determined that DCs respond to the geometry of printed ligand. Finally, we used a variety of small molecule inhibitors to identify pathways involved in geometry sensing. We saw a significant role for myosin contractility and α5β1 integrin engagement. We also noted significant reorganization of the actin cytoskeleton into dynamic actin rings when DCs were motile on posts. From these experiments, we conclude that DCs are insensitive to substrate compliance in the range tested but respond to changes in geometry via a mechanism that involves integrin function, myosin contractility, and remodeling of the actin cytoskeleton. As a possible explanation, we postulate a consistent role for filopodial extension and contraction as the driver of DC motility.
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造血谱系细胞特异性蛋白 1 与 Wiskott-Aldrich 综合征蛋白协同作用，促进树突状细胞中的足小体阵列组织和趋化性。
DOI：
10.4049/jimmunol.1003102
发表时间：
2011-04-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Dehring DA;Clarke F;Ricart BG;Huang Y;Gomez TS;Williamson EK;Hammer DA;Billadeau DD;Argon Y;Burkhardt JK
通讯作者：
Burkhardt JK
影响因子：
21.3
作者：
Vargas P;Maiuri P;Bretou M;Sáez PJ;Pierobon P;Maurin M;Chabaud M;Lankar D;Obino D;Terriac E;Raab M;Thiam HR;Brocker T;Kitchen-Goosen SM;Alberts AS;Sunareni P;Xia S;Li R;Voituriez R;Piel M;Lennon-Duménil AM
通讯作者：
Lennon-Duménil AM
影响因子：
5.6
作者：
Eroshenko N;Ramachandran R;Yadavalli VK;Rao RR
通讯作者：
Rao RR
影响因子：
21.3
作者：
Renkawitz, Joerg;Schumann, Kathrin;Sixt, Michael
通讯作者：
Sixt, Michael
影响因子：
4.3
作者：
Cox TR;Erler JT
通讯作者：
Erler JT