Leader cells mechanically respond to aligned collagen architecture to direct collective migration

• Published in: PloS one 2024-01, Vol.19 (1), p.e0296153-e0296153
• Main Authors: Lichtenberg, Jessanne Y, Ramamurthy, Ella, Young, Anna D, Redman, Trey P, Leonard, Corinne E, Das, Swadesh K, Fisher, Paul B, Lemmon, Christopher A, Hwang, Priscilla Y
• Format: Article
• Language: English
• Subjects: Biology and Life Sciences; Breast cancer; Carcinogenesis; Carcinogens; Care and treatment; Cell adhesion & migration; Cell migration; Cell Movement; Collagen; Collagen - pharmacology; Development and progression; Diagnosis; Extracellular matrix; Fibers; Gene expression; Health aspects; Hydrogels; Integrins; Mechanical analysis; Mechanical stimuli; Medicine and Health Sciences; Metastases; Metastasis; Microenvironments; Phenotypes; Physical Sciences; Research and Analysis Methods; Traction force; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0296153

Leader cells direct collective migration through sensing cues in their microenvironment to determine migration direction. The mechanism by which leader cells sense the mechanical cue of organized matrix architecture culminating in a mechanical response is not well defined. In this study, we investigated the effect of organized collagen matrix fibers on leader cell mechanics and demonstrate that leader cells protrude along aligned fibers resulting in an elongated phenotype of the entire cluster. Further, leader cells show increased mechanical interactions with their nearby matrix compared to follower cells, as evidenced by increased traction forces, increased and larger focal adhesions, and increased expression of integrin-α2. Together our results demonstrate changes in mechanical matrix cues drives changes in leader cell mechanoresponse that is required for directional collective migration. Our findings provide new insights into two fundamental components of carcinogenesis, namely invasion and metastasis.