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Cellular and Molecular Bioengineering

Cellular and Molecular Bioengineering Undergraduate Fire Talks

The regulation of fibroblast cell metabolism by migration state

Saturday, October 11, 2025

9:20 AM - 9:25 AM PDT

Location: Room 33B

Presenting Author(s)

Bryleigh Wickham

Student
Louisiana Tech University
West Monroe, Louisiana, United States

Co-Author(s)

Seth Martin

Graduate Assistant
University of Arkansas
Farmington, Arkansas, United States

Primary Investigator(s)

Jian Zhang, PhD

Assistant Professor
University of Arkansas, United States

Introduction: :

Introduction: Cell migration is important in physiological processes like wound healing and pathological processes such as excessive matrix deposition [1] and cancer cell metastasis [2], whereas the impairment of cell migration may lead to functional defects such as impaired odor-sensing abilities of neural cells [3]. Cell migration is a multi-step process that is known to consume ATP energy [4], and irregular metabolic activity during fibroblast migration and wound healing can lead to fibrosis [5]. When navigating in vivo, cells dynamically adapt their traction force generation [6] and energy production [2] to the local microenvironments, which may result in different migration rates or temporary restriction of migration. The migration state of fibroblasts was found to in turn regulate their traction force production. However, it is not clear if and how different migration states can influence the bioenergetics of the cells. Here, we engineered a microenvironment to either allow or restrict fibroblast migration on 2D surfaces and investigated the effects of migration on single-cell mitochondrial reprogramming and activity. This study provides insight into how cells regulate metabolic activity in response to their environment.

Materials and

Methods: : Materials and

Methods: To control the migration state, NIH-3T3 fibroblast cells were seeded onto micropatterned teardrop shapes on 2D glass slides coated with gelatin. The teardrop area confines cells and prevents free migration, creating a non-migrating state, and ensures the non-migrating cells have similar morphologies to migrating cells (Fig. 1A-B). Cells seeded on non-patterned areas can migrate freely and were used as the control condition. To measure the mitochondrial membrane potential (MMP), the fluorescent dye tetramethylrhodamine methyl ester (TMRM) was added to the cells. The cells were imaged using an LSM900 confocal microscope at 15 hours post-seeding.

Results, Conclusions, and Discussions::

Results: We found non-migrating NIH-3T3 cells confined on 900-µm2 teardrop patterns to have increased MMP (measured by TMRM intensity) compared to freely migrating cells (Fig. 1C-D). However, we also noticed that the TMRM intensity of migrating cells negatively correlated with their spreading area, and that the average spreading area of migrating cells was much higher than that of non-migrating cells (Fig. 1E-F). It suggests that our observed MMP differences between migrating and non-migrating cells may be attributed to their differences in spreading areas. To test this hypothesis, we selected freely migrating cells with a spreading area from 700 µm2 to 1100 µm2 and compared them with the non-migrating cells. The selected migrating cells had a comparable average spreading area to the non-migrating ones (Fig. 1E). Interestingly, we still saw a significantly increased MMP measurement in the non-migrating cells, even when compared to the selected migrating cells only (Fig. 1D), suggesting that it is indeed the migrating state of the cells that caused the different mitochondrial activity we observed.
Discussions: Confined non-migrating cells show increased intensity of TMRM fluorescence compared to migrating cells, which demonstrates that migration state regulates mitochondrial activity in fibroblast cells. This is consistent with previous work with MDA-MB-231 human breast cancer cells on square micropatterns [4]. This may suggest a non-cell-type-specific or universal mechanism of migration state regulating mitochondrial bioenergetics.

Conclusions: Confinement and prevention of migration of fibroblast cells leads to an increase in MMP and, consequently, an increase in mitochondrial activity. This finding presents insight into how cells regulate metabolism in response to their environment.

Acknowledgements and/or References (Optional): : 1. Tschumperlin DJ. Fibroblasts and the ground they walk on. Physiology (Bethesda). 2013 Nov;28(6):380-90. doi: 10.1152/physiol.00024.2013. PMID: 24186933; PMCID: PMC3858213.
2. Bergers G, Fendt SM. The metabolism of cancer cells during metastasis. Nat Rev Cancer. 2021 Mar;21(3):162-180. doi: 10.1038/s41568-020-00320-2. Epub 2021 Jan 18. PMID: 33462499; PMCID: PMC8733955.
3. Esteve D, Molina-Navarro MM, Giraldo E, Martínez-Varea N, Blanco-Gandia MC, Rodríguez-Arias M, García-Verdugo JM, Viña J, Lloret A. Adult Neural Stem Cell Migration Is Impaired in a Mouse Model of Alzheimer's Disease. Mol Neurobiol. 2022 Feb;59(2):1168-1182. doi: 10.1007/s12035-021-02620-6. Epub 2021 Dec 11. PMID: 34894324; PMCID: PMC8857127.
4. Wu Y, Zanotelli MR, Zhang J, Reinhart-King CA. Matrix-driven changes in metabolism support cytoskeletal activity to promote cell migration. Biophys J. 2021 May 4;120(9):1705-1717. doi: 10.1016/j.bpj.2021.02.044. Epub 2021 Mar 9. PMID: 33705759; PMCID: PMC8204337.
5. Yakupova EI, Zorov DB, Plotnikov EY. Bioenergetics of the Fibrosis. Biochemistry (Mosc). 2021 Dec;86(12):1599-1606. doi: 10.1134/S0006297921120099. PMID: 34937539.
6. Chang SS, Rape AD, Wong SA, Guo WH, Wang YL. Migration regulates cellular mechanical states. Mol Biol Cell. 2019 Dec 15;30(26):3104-3111. doi: 10.1091/mbc.E19-02-0099. Epub 2019 Nov 6. PMID: 31693433; PMCID: PMC6938245.