Devlog #62 – Wave 42: Cytoskeleton, Cell Signaling & Immune Response

Release Stats

New Simulations

Cytoskeleton & Cell Motility

Cell crawling is one of the most complex mechanical processes in biology. It requires the coordinated activity of hundreds of actin filaments, dozens of molecular motors, and hundreds of adhesion complexes — all operating on timescales from milliseconds to minutes. The simulation distils this into three key processes: protrusion (actin polymerization at the leading edge), adhesion (focal adhesion complex formation at the cell base), and retraction (myosin II contraction of stress fibers pulling the rear forward).

Actin filament treadmilling is the fundamental engine: at the barbed (plus) end, ATP-actin subunits add at a rate proportional to the local monomer concentration; at the pointed (minus) end, ADP-actin dissociates. When polymerization at the barbed end meets resistance (the cell membrane), the resulting force — the polymerization ratchet — pushes the membrane outward, generating the lamellipodia.

Technical details

• Cell outline rendered as a smooth closed spline with a slight wobble driven by the protrusion rate. Lamellipodia protrudes ~30 px in the direction of the signal gradient (adjustable via slider).
• 90 filament segments updated per frame: each has a growth tip that polymerizes (tip.len += k_on * ATP * dt) and retracts (tip.len -= k_off * dt). Filaments that reach zero length are removed; new ones nucleate at the leading edge.
• 24 myosin II motors interpolate along stress fibers over 600-frame lifetimes, applying a visible sliding force (shown as fiber colour shift amber→orange when myosin activity is high).
• Cell velocity is computed as v = v_protrusion − v_retraction, reported in µm/min (normalised units). Typical crawling cells move 0.1–1 µm/min in vivo.
• Right panel shows a 175×120 time-series graph of cell velocity alongside six real-time stats: protrusion rate, retraction rate, active filaments, motor activity, adhesion count, and ATP usage.

Cell Signaling Cascade (MAPK/ERK)

Signal transduction cascades achieve two remarkable feats: extreme amplification (one receptor → many effectors) and sharp threshold (switch-like) responses. The MAPK/ERK cascade is the best-studied example and controls cell proliferation, differentiation, and survival.

When EGF binds its receptor EGFR, the receptor dimerises and auto-phosphorylates on multiple tyrosine residues. This recruits adapter proteins Grb2 and SOS, which catalyse GDP→GTP exchange on the small GTPase Ras. Active Ras-GTP recruits Raf to the membrane, where it phosphorylates MEK on two serine residues. Doubly-phosphorylated MEK then phosphorylates ERK on threonine and tyrosine, producing active ERK**. The combination of two required phosphorylation steps at MEK→ERK creates a Hill coefficient of ~2, giving the cascade its switch-like dose-response.

Technical details

• Concentrations tracked as normalised fractions 0–1. ODE system stepped with Euler integration at dt = 0.04 per animation frame (effectively ~2.4 s/frame of biological time).
• Hill kinetics: [ERK*] = [MEK**]² / (Km² + [MEK**]²) with K_m = 0.4 and cooperative exponent n = 2.
• Scaffold protein KSR is modelled as a multiplicative efficiency factor: rate × (1 + scaffold × 1.2), matching experimental data showing up to 2× rate enhancement.
• Negative feedback: active ERK phosphorylates and inhibits SOS (the Ras-GEF), modelled as ligandFrac × (1 − feedback × fbStrength × 0.6).
• Animated signal particles travel along each cascade arrow at probability proportional to the upstream node's activity level. Inactive (feedback) particles are rendered at 40% opacity.
• 220×240 px time series shows Ras-GTP, MEK**, and ERK** simultaneously, making it easy to see the delay (phase lag) between upstream and downstream nodes.

Immune Response

The simulation is an agent-based model (ABM) running directly in HTML5 Canvas 2D. Agents belong to five types — pathogen, neutrophil, macrophage, T-cell, and antibody — each with distinct speed, size, and kill probability. The pathogen follows logistic growth capped by virulence; immune cells are recruited in three timed phases matching the biology:

• Immediate (0–80 ticks): Complement and mast cell signals recruit neutrophils.
• Innate (80–250 ticks): Macrophages arrive, phagocytose pathogens, and present antigens.
• Adaptive (>180 ticks): T-cells expand clonally; antibodies (B-cell derived) are secreted — or earlier if the host is vaccinated.

Technical details

• Up to ~400 live agents at any time. Each frame runs an O(n) movement pass then an O(n²) collision pass (at dt = 2 frames for physics, 1 frame for rendering) to detect kills.
• Kill probability per collision: neutrophil 3–7%, macrophage 2.5–6%, T-cell 4–9%, antibody 5–11% (scaled with immune strength slider).
• Pathogen replication: every 40 ticks, if below carrying capacity 5 + virulence×95, a daughter pathogen spawns adjacent to a parent agent.
• Each immune cell type has a lifespan: neutrophils 900 ticks, macrophages 2000, T-cells 2800, antibodies 1600 — reflecting biological half-lives.
• Vaccination fast-tracks adaptive immunity: 12 T-cells spawn at t = 10 ticks (vs. t = 180 for unvaccinated), and antibody production begins at t = 60 (vs. 240).
• Right panel: 185×195 px population history graph plots pathogen count, neutrophil count, and T-cell count simultaneously on a shared auto-scaled y-axis.

New Categories

Wave 42 introduces two new simulation categories to the platform: Cell Biology (cytoskeleton, cell-signaling) and Immunology (immune-response). These categories were previously empty gaps in the platform's spectrum coverage. Cell biology and immunology together represent a large part of modern medical research, and interactive simulations provide intuition that static diagrams cannot — seeing a lamellipodia push forward or watching pathogens get engulfed by neutrophils makes abstract mechanisms visceral.

Technical Notes

All three simulations are pure HTML5/Canvas 2D, zero external dependencies. The cytoskeleton and immune response use requestAnimationFrame loops at native display refresh rate. The cell signaling ODE integrates in under 0.05 ms per frame (Euler, 6 coupled variables). The immune response ABM runs two-frame physics skipping to maintain 60 fps even with 400 agents; the O(n²) collision detection remains fast because the agent count is capped and the inner loop exits early on dead agents.

All six files (three EN + three UK) follow the standard simulation file layout: dark canvas region + right-panel stats + control sliders + preset buttons + fact chips + formula box + info panel. Ukrainian translations are complete including all UI labels, preset names, legend text, and the educational info panel.

Tags

Cell Biology Cytoskeleton Actin Myosin Treadmilling Lamellipodia MAPK ERK Signal Cascade Hill Kinetics Immunology Neutrophil Macrophage T-cell Agent-Based Model Vaccination Wave 42