Sicard Delphine, Fredenburgh Laura E, Tschumperlin Daniel J
Department of Physiology & Biomedical Engineering, College of Medicine, Mayo Clinic, 200 1st St SW, Rochester, MN 55906, USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, 75 Francis St, Boston, MA 02115, USA.
J Mech Behav Biomed Mater. 2017 Oct;74:118-127. doi: 10.1016/j.jmbbm.2017.05.039. Epub 2017 May 31.
The mechanical properties of pulmonary tissues are important in normal function and the development of diseases such as pulmonary arterial hypertension. Hence it is critical to measure lung tissue micromechanical properties as accurately as possible in order to gain insight into the normal and pathological range of tissue stiffness associated with development, aging and disease processes. In this study, we used atomic force microscopy (AFM) micro-indentation to characterize the Young's modulus of small human pulmonary arteries (vessel diameter less than 100µm), and examined the influence of AFM tip geometry and diameter, lung tissue section thickness and the range of working force applied to the sample on the measured modulus. We observed a significant increase of the measured Young's modulus of pulmonary vessels (one order of magnitude) associated with the use of a pyramidal sharp AFM tips (20nm radius), compared to two larger spherical tips (1 and 2.5µm radius) which generated statistically indistinguishable results. The effect of tissue section thickness (ranging from 10 to 50 μm) on the measured elastic modulus was relatively smaller (<1-fold), but resulted in a significant increase in measured elastic modulus for the thinnest sections (10 μm) relative to the thicker (20 and 50 μm) sections. We also found that the measured elastic modulus depends modestly (again <1-fold), but significantly, on the magnitude of force applied, but only on thick (50 μm) and not thin (10 μm) tissue sections. Taken together these results demonstrate a dominant effect of indenter shape/radius on the measured elastic modulus of pulmonary arterial tissues, with lesser effects of tissue thickness and applied force. The results of this study highlight the importance of AFM parameter selection for accurate characterization of pulmonary arterial tissue mechanical properties, and allow for comparison of literature values for lung vessel tissue mechanical properties measured by AFM across a range of indenter and indentation parameters.
肺组织的力学性能在正常功能以及诸如肺动脉高压等疾病的发展过程中至关重要。因此，尽可能准确地测量肺组织的微观力学性能对于深入了解与发育、衰老和疾病进程相关的组织硬度的正常和病理范围至关重要。在本研究中，我们使用原子力显微镜（AFM）微压痕技术来表征小型人类肺动脉（血管直径小于100μm）的杨氏模量，并研究了AFM针尖几何形状和直径、肺组织切片厚度以及施加于样品的工作力范围对测量模量的影响。我们观察到，与两个较大的球形针尖（半径分别为1和2.5μm）相比，使用锥形尖锐AFM针尖（半径20nm）时，肺动脉血管的测量杨氏模量显著增加（一个数量级），而使用两个较大球形针尖时得到的结果在统计学上无显著差异。组织切片厚度（范围为10至50μm）对测量弹性模量的影响相对较小（<1倍），但相对于较厚（20和50μm）的切片，最薄切片（10μm）的测量弹性模量显著增加。我们还发现，测量的弹性模量适度（同样<1倍）但显著地取决于施加力的大小，但仅对厚（50μm）组织切片有影响，对薄（10μm）组织切片无影响。综合这些结果表明，压头形状/半径对肺动脉组织测量弹性模量有主导作用，而组织厚度和施加力的影响较小。本研究结果突出了AFM参数选择对于准确表征肺动脉组织力学性能的重要性，并允许比较通过AFM在一系列压头和压痕参数下测量的肺血管组织力学性能的文献值。
