Introduction
Cells are the fundamental units of life and active physical entities, constantly generating and responding to mechanical forces. This concept, known as cell force, describes the physical pushes and pulls that cells exert on their surroundings and each other. These forces are precisely controlled operations that guide how tissues are formed, how wounds heal, and how organs function. Understanding these cellular forces is key to grasping the physical principles that govern biology, from development to the onset of disease.
The Cellular Machinery of Force
A cell’s ability to generate force originates from a dynamic internal network called the cytoskeleton. This framework of protein filaments acts as the cell’s skeleton, providing structural support, and its muscle, creating movement. The primary components responsible for force generation are actin filaments and myosin motors. They work together through actomyosin contractility, a mechanism found in nearly all animal cells.
Actin filaments are dynamic cables that form a web throughout the cell, constantly assembling and disassembling to allow changes in shape. The force itself is produced by myosin motors, which function like molecular engines. These proteins use chemical energy from ATP to “walk” along actin filaments, pulling them closer together. This action creates the tensile forces that allow a cell to contract, move, and interact with its environment. The specific architecture of the actin network regulates the magnitude and direction of these forces.
Sensing and Responding to the Environment
Cells not only generate force but also sense and react to the physical characteristics of their environment. This process, called mechanotransduction, involves converting a physical force into a biochemical signal. Cells can “feel” their surroundings, detecting properties like the stiffness of the extracellular matrix (ECM)—the non-cellular network surrounding them.
Key sensors in this process are transmembrane proteins called integrins, which physically link the cell’s internal cytoskeleton to the external ECM. When a cell pulls on its surroundings, the resistance it feels is transmitted through these integrins back into the cell. This physical tug triggers a cascade of chemical signals that influence cellular decisions. For instance, a cell can determine if it is on a rigid surface like bone or a soft one like brain tissue and adapt its behavior.
This feedback loop is a constant dialogue between the cell and its environment. The forces a cell perceives can dictate its fate, determining whether it should divide, migrate, or change shape. Some mechanotransduction pathways involve proteins like YAP and TAZ, which move into the nucleus in response to high mechanical stress. Once there, they activate genes associated with cell proliferation and growth, allowing cells to adapt their function to the physical context of their tissue.
Collective Cell Behavior and Tissue Formation
During development, single-cell forces scale up as groups of cells work together to build tissues and organs. This collective behavior is responsible for the complex movements that shape the body plan. Sheets of epithelial cells can coordinate their pushing and pulling forces to fold and bend, forming structures like the neural tube, which gives rise to the brain and spinal cord.
Cell migration is another area where collective forces are apparent. Cells often travel in coordinated groups, maintaining connections with their neighbors. This is seen in the migration of neural crest cells, which journey through the embryo to form parts of the nervous system and facial skeleton. These cells move as cohesive cohorts, using cell-to-cell junctions to communicate and coordinate their direction. This movement involves “leader” cells forging a path while “follower” cells maintain group integrity, ensuring the collective moves as a single, functional unit.
Implications in Disease and Healing
The regulation of cellular forces is necessary for maintaining health, and its dysregulation is a feature of many diseases. In wound healing, cells use force in a regulated way. Fibroblasts, a type of connective tissue cell, migrate into the wound site and pull the edges of the tissue together. These fibroblasts differentiate into more contractile cells called myofibroblasts, which generate the strong tensile forces needed for repair.
When this regulation fails, the consequences can be serious. In diseases characterized by fibrosis, such as liver cirrhosis, fibroblasts become persistently activated. These cells exert excessive force, leading to the overproduction and contraction of stiff scar tissue. This matrix stiffening impairs organ function and creates a feedback loop, as the rigid environment further stimulates the force-generating cells.
The mechanics of cell force are also exploited in cancer. To metastasize, cancer cells must break free from a primary tumor and invade surrounding tissues. This process involves generating abnormal forces and recruiting cancer-associated fibroblasts (CAFs). These CAFs remodel the surrounding ECM, creating a stiffer environment and linearized “tracks” that can facilitate tumor cell invasion. The increased mechanical stress within solid tumors can also promote the survival of more aggressive cancer cells, contributing to disease progression.