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Register a new userA Bayesian traction force microscopy method with automated denoising in a user-friendly software package
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Adherent biological cells generate traction forces on a substrate that play a central role for migration, mechanosensing, differentiation, and collective behavior. The established method for quantifying this cell-substrate interaction is traction force microscopy (TFM). In spite of recent advancements, inference of the traction forces from measurements remains very sensitive to noise. However, suppression of the noise reduces the measurement accuracy and the spatial resolution, which makes it crucial to select an optimal level of noise reduction. Here, we present a fully automated method for noise reduction and robust, standardized traction-force reconstruction. The method, termed Bayesian Fourier transform traction cytometry, combines the robustness of Bayesian L2 regularization with the computation speed of Fourier transform traction cytometry. We validate the performance of the method with synthetic and real data. The method is made freely available as a software package with a graphical user-interface for intuitive usage.
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Adherent cells exert traction forces on to their environment, which allows them to migrate, to maintain tissue integrity, and to form complex multicellular structures. This traction can be measured in a perturbation-free manner with traction force microscopy (TFM). In TFM, traction is usually calculated via the solution of a linear system, which is complicated by undersampled input data, acquisition noise, and large condition numbers for some methods. Therefore, standard TFM algorithms either employ data filtering or regularization. However, these approaches require a manual selection of filter- or regularization parameters and consequently exhibit a substantial degree of subjectiveness. This shortcoming is particularly serious when cells in different conditions are to be compared because optimal noise suppression needs to be adapted for every situation, which invariably results in systematic errors. Here, we systematically test the performance of new methods from computer vision and Bayesian inference for solving the inverse problem in TFM. We compare two classical schemes, L1- and L2-regularization, with three previously untested schemes, namely Elastic Net regularization, Proximal Gradient Lasso, and Proximal Gradient Elastic Net. Overall, we find that Elastic Net regularization, which combines L1 and L2 regularization, outperforms all other methods with regard to accuracy of traction reconstruction. Next, we develop two methods, Bayesian L2 regularization and Advanced Bayesian L2 regularization, for automatic, optimal L2 regularization. Using artificial data and experimental data, we show that these methods enable robust reconstruction of traction without requiring a difficult selection of regularization parameters specifically for each data set. Thus, Bayesian methods can mitigate the considerable uncertainty inherent in comparing cellular traction forces.
Forest management relies on the evaluation of silviculture practices. The increase in natural risk due to climate change makes it necessary to consider evaluation criteria that take natural risk into account. Risk integration in existing software requires advanced programming skills.We propose a user-friendly software to simulate even-aged and monospecific forest at the stand level, in order to evaluate and optimize forest management. The software gives the possibility to run management scenarii with or without considering the impact of natural risk. The control variables are the dates and rates of thinning and the cutting age.The risk model is based on a Poisson processus. The Faustmann approach, including tree damage risk, is used to evaluate future benefits, economic or ecosystem services. It relies on the calculation of expected values, for which a dedicated mathematical development has been done. The optimized criteria used to evaluate the various scenarii are the Faustmann value and the Averaged yield value.We illustrate the approach and the software on two case studies: economic optimization of a beech stand and carbon sequestration optimization of a pine stand.Software interface makes it easy for users to write their own (growth-tree damage-economic) models without advanced programming skills. The possibility to run management scenarii with/without considering the impact of natural risk may contribute improving silviculture guidelines and adapting them to climate change. We propose future lines of research and improvement.
Atomic force microscopy (AFM) with molecule-functionalized tips has emerged as the primary experimental technique for probing the atomic structure of organic molecules on surfaces. Most experiments have been limited to nearly planar aromatic molecules, due to difficulties with interpretation of highly distorted AFM images originating from non-planar molecules. Here we develop a deep learning infrastructure that matches a set of AFM images with a unique descriptor characterizing the molecular configuration, allowing us to predict the molecular structure directly. We apply this methodology to resolve several distinct adsorption configurations of 1S-camphor on Cu(111) based on low-temperature AFM measurements. This approach will open the door to apply high-resolution AFM to a large variety of systems for which routine atomic and chemical structural resolution on the level of individual objects/molecules would be a major breakthrough.
The phenomenological model for cell shape deformation and cell migration (Chen et.al. 2018; Vermolen and Gefen 2012) is extended with the incorporation of cell traction forces and the evolution of cell equilibrium shapes as a result of cell differentiation. Plastic deformations of the extracellular matrix are modelled using morphoelasticity theory. The resulting partial differential differential equations are solved by the use of the finite element method. The paper treats various biological scenarios that entail cell migration and cell shape evolution. The experimental observations in Mak et.al. (2013), where transmigration of cancer cells through narrow apertures is studied, are reproduced using a Monte Carlo framework.
Common Spacial Patterns (CSP) is a widely used method to analyse electroencephalography (EEG) data, concerning the supervised classification of brains activity. More generally, it can be useful to distinguish between multivariate signals recorded during a time span for two different classes. CSP is based on the simultaneous diagonalization of the average covariance matrices of signals from both classes and it allows to project the data into a low-dimensional subspace. Once data are represented in a low-dimensional subspace, a classification step must be carried out. The original CSP method is based on the Euclidean distance between signals and here, we extend it so that it can be applied on any appropriate distance for data at hand. Both, the classical CSP and the new Distance-Based CSP (DB-CSP) are implemented in an R package, called dbcsp.
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