Suñé-Auñón Alejandro, Jorge-Peñas Alvaro, Aguilar-Cuenca Rocío, Vicente-Manzanares Miguel, Van Oosterwyck Hans, Muñoz-Barrutia Arrate
Bioengineering and Aerospace Engineering Department, Universidad Carlos III de Madrid, Leganés, Spain.
Instituto de Investigación Sanitaria Gregorio Marañón, 28911, Madrid, Spain.
BMC Bioinformatics. 2017 Aug 10;18(1):365. doi: 10.1186/s12859-017-1771-0.
Traction Force Microscopy (TFM) is a widespread technique to estimate the tractions that cells exert on the surrounding substrate. To recover the tractions, it is necessary to solve an inverse problem, which is ill-posed and needs regularization to make the solution stable. The typical regularization scheme is given by the minimization of a cost functional, which is divided in two terms: the error present in the data or data fidelity term; and the regularization or penalty term. The classical approach is to use zero-order Tikhonov or L-regularization, which uses the L-norm for both terms in the cost function. Recently, some studies have demonstrated an improved performance using L-regularization (L-norm in the penalty term) related to an increase in the spatial resolution and sensitivity of the recovered traction field. In this manuscript, we present a comparison between the previous two regularization schemes (relying in the L-norm for the data fidelity term) and the full L-regularization (using the L-norm for both terms in the cost function) for synthetic and real data.
Our results reveal that L-regularizations give an improved spatial resolution (more important for full L-regularization) and a reduction in the background noise with respect to the classical zero-order Tikhonov regularization. In addition, we present an approximation, which makes feasible the recovery of cellular tractions over whole cells on typical full-size microscope images when working in the spatial domain.
The proposed full L-regularization improves the sensitivity to recover small stress footprints. Moreover, the proposed method has been validated to work on full-field microscopy images of real cells, what certainly demonstrates it is a promising tool for biological applications.
牵引力显微镜技术(TFM)是一种广泛应用的技术,用于估计细胞对周围基质施加的牵引力。为了恢复牵引力,有必要解决一个不适定的反问题,这需要正则化来使解决方案稳定。典型的正则化方案是通过最小化一个代价泛函来给出的,该代价泛函分为两项:数据中存在的误差或数据保真度项;以及正则化或惩罚项。经典方法是使用零阶蒂霍诺夫正则化或L正则化,它在代价函数的两项中都使用L范数。最近,一些研究表明,使用与恢复的牵引力场的空间分辨率和灵敏度增加相关的L正则化(惩罚项中的L范数)可以提高性能。在本论文中,我们对前两种正则化方案(数据保真度项依赖于L范数)和全L正则化(代价函数的两项都使用L范数)在合成数据和真实数据上进行了比较。
我们的结果表明,与经典的零阶蒂霍诺夫正则化相比,L正则化给出了更高的空间分辨率(对全L正则化更重要)并降低了背景噪声。此外,我们提出了一种近似方法,当在空间域中工作时,它使得在典型的全尺寸显微镜图像上恢复整个细胞的细胞牵引力变得可行。
所提出的全L正则化提高了恢复小应力足迹的灵敏度。此外,所提出的方法已被验证可用于真实细胞的全场显微镜图像,这无疑证明了它是一种有前途的生物学应用工具。