Uncertainty-aware traction force microscopy

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Publicado en:PLoS Computational Biology vol. 21, no. 6 (Jun 2025), p. e1013079-e1013111
Autor principal: Kandasamy, Adithan
Otros Autores: Yi-Ting Yeh, Serrano, Ricardo, Mercola, Mark, del Alamo, Juan C
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Public Library of Science
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024 7 |a 10.1371/journal.pcbi.1013079  |2 doi 
035 |a 3270579752 
045 2 |b d20250601  |b d20250630 
084 |a 174831  |2 nlm 
100 1 |a Kandasamy, Adithan 
245 1 |a Uncertainty-aware traction force microscopy 
260 |b Public Library of Science  |c Jun 2025 
513 |a Journal Article 
520 3 |a Traction Force Microscopy (TFM) is a versatile tool to quantify cell-exerted forces by imaging and tracking fiduciary markers embedded in elastic substrates. The computations involved in TFM are often ill-conditioned, and data smoothing or regularization is required to avoid overfitting the noise in the tracked displacements. Most TFM calculations depend critically on the heuristic selection of regularization (hyper-) parameters affecting the balance between overfitting and smoothing. However, TFM methods rarely estimate or account for measurement errors in substrate deformation to adjust the regularization level accordingly. Moreover, there is a lack of tools for uncertainty quantification (UQ) to understand how these errors propagate to the recovered traction stresses. These limitations make it difficult to interpret the TFM readouts and hinder comparing different experiments. This manuscript presents an uncertainty-aware TFM technique that estimates the variability in the magnitude and direction of the traction stress vector recovered at each point in space and time of each experiment. In this technique, a non-parametric bootstrap method perturbs the cross-correlation functional of Particle Image Velocimetry (PIV) to assess the uncertainty of the measured deformation. This information is passed on to a hierarchical Bayesian TFM framework with spatially adaptive regularization that propagates the uncertainty to the traction stress readouts (TFM-UQ). We evaluate TFM-UQ using synthetic datasets with prescribed image quality variations and demonstrate its application to experimental datasets. These studies show that TFM-UQ bypasses the need for subjective regularization parameter selection and locally adapts smoothing, outperforming traditional regularization methods. They also illustrate how uncertainty-aware TFM tools can be used to objectively choose key image analysis parameters like PIV window size. We anticipate that these tools will allow for decoupling biological heterogeneity from measurement variability and facilitate automating the analysis of large datasets by parameter-free, input data-based regularization. 
610 4 |a National Institutes of Health 
651 4 |a United States--US 
653 |a Software 
653 |a Particle image velocimetry 
653 |a Decoupling 
653 |a Traction force 
653 |a Optimization 
653 |a Quality control 
653 |a Image processing 
653 |a Cross correlation 
653 |a Uncertainty 
653 |a Heterogeneity 
653 |a Traction 
653 |a Regularization 
653 |a Datasets 
653 |a Smoothing 
653 |a Image analysis 
653 |a Bayesian analysis 
653 |a Inverse problems 
653 |a Experiments 
653 |a Deformation 
653 |a Tools 
653 |a Microscopy 
653 |a Data smoothing 
653 |a Statistical methods 
653 |a Regularization methods 
653 |a Errors 
653 |a Image quality 
653 |a Parameters 
653 |a Synthetic data 
653 |a Environmental 
700 1 |a Yi-Ting Yeh 
700 1 |a Serrano, Ricardo 
700 1 |a Mercola, Mark 
700 1 |a del Alamo, Juan C 
773 0 |t PLoS Computational Biology  |g vol. 21, no. 6 (Jun 2025), p. e1013079-e1013111 
786 0 |d ProQuest  |t Health & Medical Collection 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3270579752/abstract/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text  |u https://www.proquest.com/docview/3270579752/fulltext/embedded/6A8EOT78XXH2IG52?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3270579752/fulltextPDF/embedded/6A8EOT78XXH2IG52?source=fedsrch