Mechanical strain induces involution-associated events in mammary epithelial cells

Area of Science:

• Cell Biology
• Biomechanical Engineering
• Mammary Gland Physiology

Background:

• Mammary gland involution involves epithelial apoptosis after weaning, potentially initiated by mechanical stress from milk accumulation.
• Previous studies linked mechanical stress to adaptive cell responses, but its specific role in mammary gland remodeling was unexplored.
• This study investigates the impact of mechanical stress on mammary epithelial cell physiology.

Purpose of the Study:

• To evaluate the effects of radial stretching on mammary epithelial cells in culture.
• To develop and validate a device for applying and measuring mechanical stress on cells.
• To elucidate the cellular mechanisms linking mechanical strain to mammary gland involution.

Main Methods:

• Designed and constructed a novel device for applying mechanical stress to cells cultured on flexible silicone membranes.
• Developed a geometrical model to predict radial strain on the substrate.
• Verified strain calculations using microscopic image analysis on HC11 mammary epithelial cells.
• Assessed cellular responses including protein phosphorylation, gene expression, and signaling pathway activation.

Main Results:

• Mechanical stress induced ERK1/2 phosphorylation and c-Fos expression in HC11 cells.
• Cell stretching triggered involution-associated events: Leukemia Inhibitory Factor (LIF) induction, STAT3 activation, and AKT phosphorylation inhibition.
• The developed device accurately applied and measured radial strain on the cell culture substrate.

Conclusions:

• Mechanical strain can induce weaning-associated events in cultured mammary epithelial cells.
• A new, practical, and affordable device facilitates the study of mechanical stress on cells.
• Mechanical stress is a relevant factor in the early post-lactation events leading to mammary gland involution.