Evidence map›Paper›PMID 41150696›Full record

ArticlePLoS computational biology2025

Inference of weak-form partial differential equations describing migration and proliferation mechanisms in wound healing experiments on cancer cells.

Siddhartha Srivastava, Patrick C Kinnunen, Zhenlin Wang, Kenneth K Y Ho, Brock A Humphries, Siyi Chen, Jennifer J Linderman, Gary D Luker, Kathryn E Luker, Krishna Garikipati

Abstract read
In one paragraph

Article in PLoS computational biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Siddhartha SrivastavaDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, United States.
Patrick C KinnunenDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States.ORCID 0000-0002-1741-2867
Zhenlin WangDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, United States.
Kenneth K Y HoDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, United States.
Brock A HumphriesDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, United States.
Siyi ChenDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, United States.
Jennifer J LindermanDepartment of Chemical Engineering, University of Michigan, Ann Arbor, Michigan, United States.ORCID 0000-0002-1519-5088
Gary D LukerDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, United States.
Kathryn E LukerDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, United States.
Krishna GarikipatiDepartment of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan, United States.ORCID 0000-0001-6697-0067

Funding

Interstitial Fluid Flow Regulates Glioma Cell InvasionR37CA222563 · NCI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI MUNSON, JENNIFER M · 2018 to 2024
$4.0M
Imaging Disease Heterogeneity and Response to Therapy in MyelofibrosisR01CA238023 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LUKER, GARY D, ROSS, BRIAN D. · 2019 to 2023
$3.1M
Integrators of Metastatic PotentialR01CA238042 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA, LUKER, GARY D · 2019 to 2023
$2.3M
Specialist in Multi-Scale Molecular Imaging of Tumor EnvironmentsR50CA221807 · NCI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Kathryn Luker · 2018 to 2026
$1.6M
A High Throughput Human Tumor Modeling Technology for Cancer Drug DiscoveryR33CA225549 · NCI · UNIVERSITY OF AKRON · PI LUKER, GARY D, TAVANA, HOSSEIN · 2019 to 2021
$1.4M
Sensing and modulating the chemokine environment with synthetic cellsR21AI173559 · NIAID · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, ALLEN PO-CHIH, LUKER, GARY D · 2023 to 2024
$429k
NCI NIH HHS R01 CA238023NCI NIH HHS R01 CA238042NCI NIH HHS R33 CA225549NCI NIH HHS R37 CA222563NCI NIH HHS R50 CA221807NIAID NIH HHS R21 AI173559
6 · The paper itself

Abstract

Cancer metastasis, which requires migration of cancer cells away from the primary tumor, is responsible for approximately 65% percent of cancer-related deaths. Therefore, targeting signaling pathways that drive cancer cell migration or proliferation is a common therapeutic approach. Cell migration is commonly studied using experimental approaches which track cells or cell monolayers as they evolve over time. Computational modeling can then be used to fit partial differential equation (PDE) models to the data, providing mechanistic insights underlying the observed cell motion, including the contribution of various cellular behaviors such as random motion, directed motion, and cell division. A popular experimental technique, the scratch assay, measures the migration and proliferation-driven cell closure of a scratch in a confluent cell monolayer. However, these assays do not disambiguate between different drivers of scratch closure (for instance between cell proliferation and migration to open space). To improve analysis of this technique, we combine scratch assays, video microscopy, and PDE inference to gain quantitative insight to mechanisms of cell migration and proliferation. We capture the evolution of cell density fields over time using live-cell microscopy and automated image processing. Our PDE inference methods involve the use of weak form-based system identification techniques for cell density dynamics modeled with advection-diffusion-reaction systems. We then compare our method with recent modeling work, finding that our model discovery tool automatically identifies similar models including reaction and diffusion terms from a larger set of bases. We demonstrate the application of this framework on 2-dimensional scratch assays subject to the inhibiting effect of trametinib on wound closure and characterize the results in the context of the quantified uncertainty in our inference approach. Our integrated experimental and computational pipeline can be used to rapidly identify and refine models of cell migration in a variety of contexts, enabling the quantitative measurement of the effect of drugs and other perturbations on cell migration and proliferation with uncertainty accounted for.

Indexed as

Cell MovementCell ProliferationModels, BiologicalNeoplasmsWound HealingCell Line, TumorComputational BiologyComputer SimulationHumans

Identifiers

PMID41150696
PMCPMC12578354

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.