7.4 Cell motility and molecular motors

Cell Motility

Cells move in several distinct ways, from crawling across surfaces to swimming through fluids. These movements drive processes like wound healing, embryonic development, and muscle contraction. The molecular machinery behind all of them relies on motor proteins that convert chemical energy (from ATP hydrolysis) into mechanical force.

Types of Cell Motility

Cell crawling involves extending the leading edge of a cell forward while retracting the trailing edge. This is how cells move across solid surfaces during wound healing and embryonic development.

Cell swimming uses cilia or flagella to propel a cell through liquid. Single-celled organisms like Paramecium use this for locomotion, while epithelial cells lining your airways use cilia to move mucus across their surface.

Cytoplasmic streaming is the directed flow of cytoplasm inside a cell, driven by the cytoskeleton. It transports organelles, vesicles, and other components to where they're needed. Plant cells rely heavily on this because of their large cell volumes.

Muscle contraction shortens muscle fibers by sliding actin and myosin filaments past each other. This generates force in skeletal muscles, the heart, and smooth muscle throughout the body.

Cell Crawling vs. Cell Swimming

These two motility modes differ in their molecular machinery, their dependence on surfaces, and their regulatory mechanisms.

• Cell crawling
  • Polymerizes actin filaments at the leading edge (pushing it forward) and contracts actin-myosin networks at the trailing edge (pulling the rear up)
  • Forms focal adhesions between the cell and the substrate to gain traction
  • Regulated by Rho GTPases and downstream signaling pathways (more on these below)
• Cell swimming
  • Coordinates the beating of cilia or flagella, which are built from microtubules arranged in a 9+2 axoneme structure with dynein motors
  • Does not require substrate adhesion
  • Powered by ATP hydrolysis driving dynein-dependent sliding of microtubule doublets, which is converted into a bending motion by structural constraints within the axoneme

Molecular Motors and Muscle Contraction

Structure and Function of Molecular Motors

Molecular motors are proteins that walk along cytoskeletal filaments, converting the energy of ATP hydrolysis into directional movement. The three major families differ in which filament they use and which direction they travel.

• Kinesins
  • Walk toward the plus end of microtubules (generally toward the cell periphery)
  • Consist of two heavy chains (each containing a motor domain) and two light chains
  • Transport organelles, vesicles, and other cargoes outward. A classic example is anterograde axonal transport in neurons, where kinesins carry synaptic vesicle precursors from the cell body to the axon terminal.
• Dyneins
  • Walk toward the minus end of microtubules (generally toward the cell center)
  • Larger and more complex than kinesins: composed of two or three heavy chains with motor domains, plus several intermediate and light chains
  • Responsible for retrograde transport of cargoes toward the cell center. Cytoplasmic dynein also positions the mitotic spindle during cell division. Axonemal dynein is the motor that drives cilia and flagella beating.
• Myosins
  • Walk along actin filaments rather than microtubules
  • Myosin II is the motor behind muscle contraction and the contractile ring during cytokinesis
  • Other myosin family members (e.g., myosin V) transport vesicles along actin tracks

All three motor families share a common principle: they hydrolyze ATP, and the conformational changes that result produce a "stepping" motion along their respective filament.

Molecular Basis of Muscle Contraction

Muscle contraction is driven by the sliding filament model, where thin (actin) and thick (myosin II) filaments slide past each other within the sarcomere. Here's how the cross-bridge cycle works:

1. A myosin head, loaded with ADP and inorganic phosphate ($P_i$), binds to an actin filament.
2. $P_i$ is released, triggering the power stroke: the myosin head pivots, pulling the actin filament toward the center of the sarcomere (the M-line).
3. ADP is released from the myosin head.
4. A new ATP molecule binds to the myosin head, causing it to detach from actin.
5. ATP is hydrolyzed to ADP + $P_i$, which re-cocks the myosin head into its high-energy conformation, ready for another cycle.

Regulation by calcium: In resting muscle, the troponin-tropomyosin complex blocks the myosin-binding sites on actin. When $Ca^{2+}$ is released from the sarcoplasmic reticulum (triggered by a nerve impulse), $Ca^{2+}$ binds to troponin C. This shifts tropomyosin out of the way, exposing the binding sites and allowing cross-bridge cycling to begin. When $Ca^{2+}$ is pumped back into the sarcoplasmic reticulum, tropomyosin re-blocks the sites and the muscle relaxes.

Cell Motility Regulation

Signaling Pathways in Cell Motility

Cell crawling doesn't happen randomly. It's tightly controlled by intracellular signaling, especially through the Rho GTPase family and focal adhesion kinase (FAK).

Rho GTPases (RhoA, Rac1, Cdc42) act as molecular switches that cycle between an active (GTP-bound) and inactive (GDP-bound) state. Each one controls a different aspect of the actin cytoskeleton:

• Cdc42 promotes the formation of filopodia (thin, finger-like protrusions that sense the environment)
• Rac1 induces lamellipodia (broad, sheet-like protrusions that drive the leading edge forward)
• RhoA promotes stress fibers and contractility at the rear of the cell, helping retract the trailing edge

These three GTPases work together to coordinate the front-to-back polarity that a crawling cell needs.

Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that becomes activated when integrins cluster at focal adhesions (the points where the cell grips the substrate). FAK plays a central role in both the formation and turnover of focal adhesions, which is critical because a crawling cell needs to make new adhesions at the front and release old ones at the back. FAK also feeds into Rho GTPase signaling, linking adhesion dynamics to cytoskeletal remodeling.