Activation effects on the physical characteristics of T lymphocytes.

Activation effects on the physical characteristics of T lymphocytes.
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DOI:
10.3389/fbioe.2023.1175570
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发表时间:
2023
影响因子:
5.7
通讯作者:
Kim, Minsoo
Kim, Minsoo
中科院分区:
工程技术2区
文献类型:
--
作者:
Waugh, Richard E.;Lomakina, Elena;Amitrano, Andrea;Kim, Minsoo

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白细胞的变形性与多种生理和病理生理行为有关。这项研究的目的是提供T细胞机械特性的详细、定量的表征,以及这些特性如何随着激活而变化。我们检测了从健康捐赠者的外周血样本中分离出来的T细胞和CD8+细胞,无论是立即(天真人群)还是在体外激活7天后。采用单细胞微吸管吸引法测试材料的力学性能。T细胞表现出具有皮质“表面”张力的高粘度液滴的一般特征,即T细胞。在两种不同的吸气压力下测量每个细胞进入微吸管的时间进程,以测试剪切变稀行为。在细胞变形的近似力学模型的框架内分析数据,以确定皮质张力、细胞体积、初始细胞进入的大小、特征粘度μo和剪切稀化系数,b.激活通常会导致细胞对变形的抵抗力增加和细胞性质的分布变宽。当细胞激活时,细胞体积从∼200xμm~3增加到∼650m~3μm~3。幼稚T细胞和活化T细胞的平均皮质张力相似(∼150pN/μm)。然而,与单纯CD8+细胞相比,活化的CD8+T细胞的皮质张力显著增加到∼250npN/μm,反映其特征粘度的动态阻力为∼870pA,体外激活后显著增加到1180pA。当细胞进入吸管(L初始)时,激活的细胞与未激活的细胞相比,瞬时投射长度增加了一倍多。所有细胞类型都表现出剪切变薄行为,其系数b在0.5-0.65的范围内。细胞大小、皮质张力和特征粘度的增加都表明激活的T细胞对通过微血管系统的抵抗力增强,这可能是细胞捕获的原因。激活后细胞的初始弹性反应增加是意想不到的,这可能表明细胞不稳定,这可能有助于细胞的自发运动。
The deformability of leukocytes is relevant to a wide array of physiological and pathophysiological behaviors. The goal of this study is to provide a detailed, quantitative characterization of the mechanical properties of T cells and how those properties change with activation. We tested T cells and CD8+ cells isolated from peripheral blood samples of healthy donors either immediately (naïve population) or after 7 days of activation in vitro. Single-cell micropipette aspiration was used to test the mechanical properties. T cells exhibit the general characteristics of a highly viscous liquid drop with a cortical “surface” tension, T cort . The time course of each cell entry into the micropipette was measured at two different aspiration pressures to test for shear thinning behavior. The data were analyzed in the framework of an approximate mechanical model of the cell deformation to determine the cortical tension, the cell volume, the magnitude of the initial cell entry, the characteristic viscosity μ o , and the shear thinning coefficient, b. Activation generally caused increases in cellular resistance to deformation and a broadening of the distribution of cell properties. The cell volume increased substantially upon cell activation from ∼200 μm3 to ∼650 μm3. Naive and activated T cells had similar mean cortical tension (∼150 pN/μm). However, compared to naïve CD8+ cells, the cortical tension of activated CD8+ cells increased significantly to ∼250 pN/μm. Dynamic resistance of naive CD8+ T cells, as reflected in their characteristic viscosity, was ∼870 Pa and significantly increased to 1,180 Pa after in vitro activation. The magnitude of the instantaneous projection length as the cell enters the pipette (L init ) was more than doubled for activated vs. naive cells. All cell types exhibited shear thinning behavior with coefficients b in the range 0.5–0.65. Increased cell size, cortical tension, and characteristic viscosity all point to increased resistance of activated T cells to passage through the microvasculature, likely contributing to cell trapping. The increased initial elastic response of cells after activation was unexpected and could point to instability in the cell that might contribute to spontaneous cell motility.
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