High Resolution, Large Deformation 3D Traction Force Microscopy

Traction Force Microscopy (TFM) is a powerful approach for quantifying cell-material interactions that over the last two decades has contributed significantly to our understanding of cellular mechanosensing and mechanotransduction. In addition, recent advances in three-dimensional (3D) imaging and traction force analysis (3D TFM) have highlighted the significance of the third dimension in influencing various cellular processes. Yet irrespective of dimensionality, almost all TFM approaches have relied on a linear elastic theory framework to calculate cell surface tractions. Here we present a new high resolution 3D TFM algorithm which utilizes a large deformation formulation to quantify cellular displacement fields with unprecedented resolution. The results feature some of the first experimental evidence that cells are indeed capable of exerting large material deformations, which require the formulation of a new theoretical TFM framework to accurately calculate the traction forces. Based on our previous 3D TFM technique, we reformulate our approach to accurately account for large material deformation and quantitatively contrast and compare both linear and large deformation frameworks as a function of the applied cell deformation. Particular attention is paid in estimating the accuracy penalty associated with utilizing a traditional linear elastic approach in the presence of large deformation gradients.

牵引力显微镜（Traction Force Microscopy, TFM）是一种用于量化细胞-材料相互作用的高效研究手段，在过去二十年间极大推动了我们对细胞机械感知与机械转导过程的认知。此外，近年来三维（3D）成像与牵引力分析技术（3D TFM）的进展，凸显了三维维度在调控各类细胞生命活动中的重要意义。然而无论维度如何，几乎所有TFM研究方法均依托线性弹性理论框架来计算细胞表面牵引力。本文提出一种全新的高分辨率3D TFM算法，该算法采用大变形公式，以前所未有的分辨率量化细胞位移场。本研究所得结果提供了首批实验证据之一，证明细胞确实能够对材料施加大变形，这一现象亟需构建全新的理论TFM框架以精准计算细胞牵引力。基于此前开发的3D TFM技术，我们对研究方法进行了重新公式化，以精准适配材料大变形场景，并基于施加的细胞变形量，对线性弹性与大变形两种理论框架进行了定量对比与分析。本研究特别关注了在存在大变形梯度的情况下，采用传统线性弹性方法所带来的精度损失问题。