Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Phys Condens Matter. 2010 May 19;22(19):194120. doi: 10.1088/0953-8984/22/19/194120. Epub 2010 Apr 26.
Mechanical properties of cells and extracellular matrices are critical determinants of function in contexts including oncogenic transformation, neuronal synapse formation, hepatic fibrosis and stem cell differentiation. The size and heterogeneity of biological specimens and the importance of measuring their mechanical properties under conditions that resemble their environments in vivo present a challenge for quantitative measurement. Centimeter-scale tissue samples can be measured by commercial instruments, whereas properties at the subcellular (nm) scale are accessible by atomic force microscopy, optical trapping, or magnetic bead microrheometry; however many tissues are heterogeneous on a length scale between micrometers and millimeters which is not accessible to most current instrumentation. The device described here combines two commercially available technologies, a micronewton resolution force probe and a micromanipulator for probing soft biological samples at sub-millimeter spatial resolution. Several applications of the device are described. These include the first measurement of the stiffness of an intact, isolated mouse glomerulus, quantification of the inner wall stiffness of healthy and diseased mouse aortas, and evaluation of the lateral heterogeneity in the stiffness of mouse mammary glands and rat livers with correlation of this heterogeneity with malignant or fibrotic pathology as evaluated by histology.
细胞和细胞外基质的力学性质是功能的关键决定因素，包括致癌转化、神经元突触形成、肝纤维化和干细胞分化等。生物样本的大小和异质性以及在类似于体内环境的条件下测量其力学性质的重要性，对定量测量提出了挑战。商业仪器可以测量厘米尺度的组织样本，而原子力显微镜、光阱或磁珠微流变仪可以测量亚细胞（nm）尺度的性质；然而，许多组织在微米到毫米之间的长度尺度上存在异质性，这是大多数现有仪器无法测量的。这里描述的设备结合了两种商业上可用的技术，即毫牛分辨率力探针和用于探测软生物样品的微操纵器，可实现亚毫米空间分辨率的探测。该设备有几个应用。其中包括首次测量完整的、分离的小鼠肾小球的刚度，量化健康和患病小鼠主动脉的内管壁刚度，以及评估小鼠乳腺和大鼠肝脏的刚度的横向异质性，并通过组织学评估与恶性或纤维化病理相关的这种异质性。
