Fig. 3

Fig. 3

Cortical Contractility Fluctuations Drive Polarization to Stable-Bleb Cells

(A) Sketch of polarization from a non-polarized state (left) to a polarized stable-bleb state (right). The cell cortex is shown in green and highly contractile cortex areas in red. Red arrows denote a cortical force imbalance due to local fluctuations in cortical contractility. Blebs induce spatial inhomogeneities in cortical contractility of increasing strength for larger bleb sizes. Green arrows indicate cortical flows.

(B) Stability diagram illustrating the switch from a non-polarized to a polarized state. The curve represents the values of cortical contractility ζ, depending on the density fluctuation mode number l. The mode number, l, is inversely proportional to the wavelength (in units of initial cell radius) of the fluctuation.

(C) Myosin II localization in a transforming progenitor cell cultured in suspension with 30 µM LPA. Scale bar represents 20 µm.

(D) Sketch of the local LPA application experiment.

(E) BF time-lapse images and Myl12.1-eGFP localization during progenitor cell polarization in a local 100 µM LPA diffusion gradient set by a micropipette (red arrow).

(F) Histogram of measured cell polarization orientations (n = 32).

(G and H) Schematic illustration of the positive feedback loop between cortical actomyosin density gradients and rearward cortical flows for the maintenance of stable-bleb cell polarity. Local fluctuations in cortical contractility induce a flow toward the contractile region along with mass transport of actin and myosin (red dots) that reinforces the initial instability (G). To maintain a continuous cortical flow in polarized cells actin turnover (with rate constants k_p and k_d) and diffusion of free actin and myosin (with diffusion constant D) is required (H). Polarization is lost upon pharmacological inhibition of myosin II contractility (by Blebbistatin), actin polymerization (by Latrunculin-A) and actin de-polymerization (by Jasplakinolide).

See also Figure S2, Movies S2 and S4, and Extended Experimental Procedures.