Tiny feet on cells can sense defects and stall migration to heal wounds
Cells travel through the body both individually and in collective groups during development, wound healing and diseases such as cancer. New research from the McKelvey School of Engineering at Washington University in St. Louis shows that cells can sense even the smallest defects, or micro-injuries, in the surface beneath which they travel and stall long enough to begin the healing process.
Cells, whether traveling individually or in groups, move through the body during various processes such as development, wound healing, and diseases like cancer. A recent study conducted by researchers at the McKelvey School of Engineering at Washington University in St. Louis reveals that cells can detect even the smallest defects, or micro-injuries, in the surface beneath them and pause long enough to initiate the healing process.
The study, published in Cell Reports on July 31, 2026, was led by Professor Amit Pathak and his team, including doctoral candidate Hannah Zmuda, who earned her degree in biomedical engineering from McKelvey Engineering in 2025.
The researchers discovered that the tiny "feet" at the leading edge of a group of cells, known as filopodia, can sense a defect as small as a few microns in the membrane beneath the extracellular matrix, which serves as structural support for cell growth and tissue regeneration. These filopodia are highly sensitive and can stop the cells for up to eight hours when collagen IV, a component of the basement membrane, is present.
However, when exposed to collagen I or stiffer extracellular matrices, the filopodia continue moving over the defect, indicating that the stiffness of the surrounding environment plays a crucial role in this sensing process.
In cancerous environments, the basement membrane is often degraded, allowing access to collagen type I, a more native tissue component. Pathak explained that if cells fail to notice small wounds and continue moving, it may indicate the absence of healing, as stalling and deposition of new extracellular matrix are necessary for wound repair.
The researchers also found that the surrounding environment significantly influences the effectiveness of this stalling response, with factors such as the stiffness of the surrounding material and the osmolarity of the fluid medium playing a role.
To conduct their research, the team used human mammary epithelial cells, Madin-Darby canine kidney cells, and primary zebrafish keratinocytes derived from fish scales. They created defects in the extracellular matrix using laser ablation and imaged cell movement using atomic force microscopy. The study highlights the importance of considering multiple extracellular cues, including protein types, stiffness, and osmotic conditions, in understanding subcellular mechanics and collective migration of cells.
This knowledge could enhance our understanding of fundamental biological processes in wound healing, development, and tumor invasion.
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