Coughlin Mark F, Puig-de-Morales Marina, Bursac Predrag, Mellema Matthew, Millet Emil, Fredberg Jeffrey J
Physiology Program, Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Biophys J. 2006 Mar 15;90(6):2199-205. doi: 10.1529/biophysj.105.061267. Epub 2005 Dec 30.
Here we report the rheological properties of cultured hsFLNa (filamin-A)-expressing (FIL+) and hsFLNa-deficient (FIL-) melanoma cells. Using magnetic twisting cytometry over a wide range of probing frequencies, and targeting either cortical or deeper cytoskeletal structures, we found that differences in stiffness of FIL+ versus FIL- cells were remarkably small. When probed through deep cytoskeletal structures, FIL+ cells were, at most, 30% stiffer than FIL- cells, whereas when probed through more peripheral cytoskeletal structures FIL- cells were not different except at very high frequencies. The loss tangent, expressed as an effective cytoskeletal temperature, was systematically greater in FIL- than FIL+ cells, but these differences were small and showed that the FIL+ cells were only slightly closer to a solidlike state. To quantify cytoskeletal remodeling, we measured spontaneous motions of beads bound to cortical cytoskeletal structures and found no difference in FIL+ versus FIL- cells. Although mechanical differences between FIL+ and FIL- cells were evident both in cortical and deeper structures, these differences were far smaller than expected based on measurements of the rheology of purified actin-filamin solutions. These findings do not rule out an important contribution of filamin to the mechanical properties of the cortical cytoskeleton, but suggest that effects of filamin in the cortex are not exerted on the length scale of the probe used here. These findings would appear to rule out any important contribution of filamin to the bulk mechanical properties of the cytoplasm, however. Although filamin is present in the cytoplasm, it may be inactive, its mechanical effects may be small compared with other crosslinkers, or mechanical properties of the matrix may be dominated by an overriding role of cytoskeletal prestress.
在此,我们报告了表达人源细丝蛋白A(hsFLNa)(FIL+)和缺乏hsFLNa(FIL-)的培养黑色素瘤细胞的流变学特性。通过在广泛的探测频率范围内使用磁扭细胞术,并针对皮质或更深层的细胞骨架结构进行探测,我们发现FIL+细胞与FIL-细胞的硬度差异非常小。当通过深层细胞骨架结构进行探测时,FIL+细胞的硬度最多比FIL-细胞高30%,而当通过更多外周细胞骨架结构进行探测时,除了在非常高的频率下,FIL-细胞没有差异。以有效细胞骨架温度表示的损耗角正切在FIL-细胞中系统性地高于FIL+细胞,但这些差异很小,表明FIL+细胞仅略微更接近固态。为了量化细胞骨架重塑,我们测量了与皮质细胞骨架结构结合的珠子的自发运动,发现FIL+细胞与FIL-细胞之间没有差异。尽管FIL+和FIL-细胞在皮质和更深层结构中的力学差异都很明显,但基于对纯化肌动蛋白-细丝蛋白溶液流变学的测量,这些差异远小于预期。这些发现并不排除细丝蛋白对皮质细胞骨架力学特性的重要贡献,但表明细丝蛋白在皮质中的作用并非在此处使用的探针长度尺度上发挥。然而,这些发现似乎排除了细丝蛋白对细胞质整体力学特性的任何重要贡献。尽管细丝蛋白存在于细胞质中,但它可能是无活性的,与其他交联剂相比其力学效应可能很小,或者基质的力学特性可能由细胞骨架预应力的主导作用所决定。