Milestones

Twenty pieces of work that changed how blebs are understood, 1755–2026.

Twenty pieces of work that changed how blebs are understood, from a drawing of 1755 to experiments of 2026. Each page sets out what was known before, what was done, what changed and what remains open. We chose work that introduced a concept, a measurement, an experimental system or a word that later work builds on; the choice is open to correction. The connecting story is in A long history of blebbing.

Seeing amoeboid movement and naming the bleb, 1755–1919

• M01 1755 Rösel's 'little Proteus', drawn changing shape established
  In 1755 Rösel von Rosenhof drew a tiny freshwater animal changing shape and splitting in two; histories treat it as the first depicted amoeboid organism.
• M02 1835–1872 Amoeboid movement becomes a property of protoplasm established
  Between 1835 and the 1860s, amoeboid movement became a behavior of naked protoplasm shared by amoebae, white blood cells and eggs, not the trait of one organism.
• M03 1893–1919 The word 'bleb' enters cell biology established
  'Bleb' first names cell-surface protrusions in passing in 1893 and 1898; Hogue (1919) gives the first definition and labeled drawings we found, for dying fibroblasts.

Pressure and gel in the amoeboid cytoplasm, 1923–1982

• M04 1923–1947 Amoeboid movement as a pressurized, contracting gel tube established
  In 1923 Mast and Pantin replaced surface tension with a contracting gel tube that pushes fluid cytoplasm forward; Mast added internal pressure and a weak, rupturing tip.
• M05 1959–1961 Streaming pressure and viscosity measured in moving amoebae strongly supported
  Around 1960, capillary and magnetic-particle methods measured the pressure that halts streaming in giant amoebae and showed a structured, non-Newtonian endoplasm; whether pressure drives streaming stayed disputed.
• M06 1982 Cytoplasm as a cross-linked actin gel: from Dujardin to the connectivity threshold strongly supported
  Pollard et al. (1982) recast contractile protoplasm as actin cross-linked above a gel point; reconstituted gels contract only within a window of cross-linking.

Blebs on cultured animal cells, 1958–1984

• M07 1958–1968 Blebs measured and modeled as pressure blow-outs strongly supported
  Blebs on cultured cells were induced, timed and sectioned, and given the earliest mathematical model of blebbing we found: membrane pushed out by pressure under Laplace's law.
• M08 1973–1975 Blebbing on living, dividing cells follows cortical contraction strongly supported
  Blebs were found on healthy cycling cells, mostly in G1, and cytochalasin D blebbing was shown to need energy-dependent cortical contraction, proposed to open gaps in the cortex.
• M09 1982–1984 Blebs anchor lymphocytes moving through 3D matrix proposed
  Lymphocytes in collagen gels advanced past blebs that stayed fixed in the matrix, suggesting blebs as anchors for adhesion-independent movement driven by a backward contraction wave.

The regulated bleb, 1995–2003

• M10 1995–1999 A bleb is membrane freed from the cortex established
  Blebs form where membrane leaves a cortex that stays behind, expand before new actin assembles and stop as it does; their low-tension membrane made them probes of tension and pressure.
• M11 1998–2003 ROCK–myosin contraction drives blebbing in dying and in invading cells strongly supported
  Blebbing of stressed and dying cells was traced to myosin II, switched on in apoptosis by caspase-cleaved ROCK I; Rho–ROCK also drives rounded, blebbing tumor invasion.

Blebs as physical objects

• M12 2005–2009 The physics of bleb growth: pressure, a poroelastic cytoplasm and a tension threshold strongly supported
  Local drug perfusion and laser ablation turned blebs into gauges of pressure and tension, revealing a poroelastic cytoplasm and a tension threshold for bleb growth.
• M13 2006–2010 Cortex reassembly and membrane–cortex attachment control blebbing strongly supported
  A retracting bleb rebuilds its cortex in a fixed order, and membrane–cortex attachment, set largely by ERM proteins, controls how often and how large cells bleb.
• M14 2016–2024 Inverse blebs: pressure from outside the cell strongly supported
  Where outside fluid is at higher pressure, the membrane bulges into the cell without actin and actomyosin retracts it: inverse blebs in vessels, embryos and liver.
• M15 2016–2026 Blebs rebuilt from purified proteins, and their two initiation routes separated strongly supported
  An actin–myosin cortex linked to the inside of a liposome is enough to make blebs, and coupling and cross-linking decide whether the cortex peels away or tears.

Blebs as signaling hubs

• M16 2023 Blebs as curvature-based signaling hubs for survival strongly supported
  In detached melanoma cells, septins gathered at curved bleb bases and scaffolded NRAS, sustaining ERK and PI3K signaling, so that blebbing supported survival.

When blebs leave the cell

• M17 1883–2025 Blebbing as a route to cell fragmentation strongly supported
  Blebs can detach as pieces of cytoplasm, usually without a nucleus, that move or carry cargo; anucleate pieces can keep blebbing, and many fragments form in other ways.

Blebs in migration

• M18 2006 Blebs drive directed migration in embryos and amoebae established
  Three 2006 studies showed that blebs are a normal, steerable, myosin-driven protrusion of chemotaxing cells, in zebrafish germ cells and Dictyostelium amoebae.
• M19 2008–2013 Blebs framed as a protrusion and migration mode of their own established
  Three reviews recast the bleb from a sign of cell death into a pressure-driven protrusion and migration mode, and set the questions the field then worked through.
• M20 2015 Confinement switches many cells to stable-bleb migration established
  Confinement, low adhesion and high contractility turn slow cells of many types into fast amoeboid cells led by one stable bleb and moved by cortical flow and friction.