Bioenergetics underlying single-cell migration on aligned nanofiber scaffolds.

Area of Science:

• Cell Biology
• Bioenergetics
• Biophysics

Background:

• Cell migration is crucial for physiological processes like wound healing and pathological conditions such as cancer metastasis.
• The bioenergetics supporting cell migration are not fully elucidated, partly due to limitations in current cell culture models.
• Understanding cellular energy metabolism during migration is key to developing targeted therapies.

Purpose of the Study:

• To investigate the bioenergetics of C2C12 myoblast migration and force production.
• To determine the contribution of glycolysis versus mitochondrial respiration to cell migration and force generation.
• To assess the impact of different culture media substrates on migratory bioenergetics.

Main Methods:

• Fabrication of fibronectin-coated nanofiber scaffolds using a spinneret-based tunable engineered parameters (STEP) platform.
• Utilized metabolic inhibitors targeting cellular respiration, ATP synthesis, glycolysis, and glucose uptake.
• Employed nanonet force microscopy to measure single-cell force production.

Main Results:

• Inhibitors of glycolysis and glucose uptake significantly reduced cell migration velocity, while mitochondrial inhibitors had a modest effect.
• Cell migration's metabolic reliance shifted when cells were cultured in galactose instead of glucose, showing sensitivity to mitochondrial inhibition.
• Neither mitochondrial nor glycolytic inhibition affected single-cell force production, suggesting migration and force generation are differentially regulated.

Conclusions:

• C2C12 myoblast migration in conventional glucose-based media is predominantly fueled by glycolysis.
• Cellular energy substrate availability significantly modulates the bioenergetic pathways driving cell migration.
• These findings have implications for understanding and therapeutically targeting cellular migration in various biological contexts.