Self-organization and Pattern Formation

Our lab discovered that membrane curvature-generating proteins in the F-BAR family—FBP17, CIP4—and the small GTPase CDC42 can form rhythmic, wave-like patterns on the surface of mast cells, a type of immune cell involved in both innate and adaptive immunity (Wu et al., PNAS 2013). In recent years waves assembled on the cortex of single cells have emerged as important organizational principle for diverse processes involving membrane-cortex remodeling, such as cell motility and polarity. The reaction-diffusion model, proposed by Alan Turing, can explain a wide variety of complex patterns with a simple system made of two interacting diffusible substances (activator and inhibitor) that have different lifetimes and diffusion rates. Specifically, periodic spatial patterns can emerge if the activator has a short range, but the inhibitor has a long range, in which case the inhibitor range specifies the length scale of the spatial pattern; oscillations will result if the inhibitor has a longer time constant than the activator, in which case the inhibitor lifetime specifies the time scale of oscillation; and traveling waves result if the activator has a moderate spread but the inhibitor is local. These mechanisms allow the system to self-organize and generate spatial and temporal patterns autonomously without any pre-patterns.

While there are conceptual models for how patterns form, it remains challenging to understand the origin and function of specific patterns in real biological systems. We aim to investigate how these patterns form on the surface of immune cells, as we believe that a deeper understanding of the underlying biological mechanisms is essential to reveal how cells might use such patterns to process information.

How do the waves propagate, and what determines or limits their propagation speed? We demonstrated that cortical waves are driven by membrane curvature changes mediated by FBP17 and CIP4 (Wu et al., Nature Communications 2018). The shallow curvature preference of the F-BAR domain is essential for wave formation, and the propagation speed of the waves is governed by the rate of these underlying shape changes. In collaboration with Jian Liu’s group at NIH, we combined experimental and computational approaches to show that membrane shape change is integral to wave propagation. The mechano-chemical model we proposed highlights curvature-mediated spatial propagation, distinguishing it from previous models of actin waves that relied on chemical diffusion alone. Because direct membrane recruitment contributes more than lateral diffusion to wave propagation, these mechanochemical waves behave as phase waves (also known as pseudo-waves or kinematic waves), which travel faster than traditional trigger waves.

We also contributed to understanding how FBP17 senses membrane curvature. Unlike other F-BAR domains, FBP17 lacks a hydrophobic insertion motif. Our work revealed that its curvature-sensing ability primarily originates from its intrinsically disordered region, rather than the folded F-BAR domain as previously assumed (Su et al., iScience, 2020).

These cortical waves are also coupled to cycles of actin and microtubule disassembly (Chua et al., Cell Reports 2024; Tong et al., 2024). In particular, Arp2/3 and formin, two major classes of actin-nucleating proteins, play both synergistic and competitive roles in fine-tuning the actin cytoskeleton (Chua et al., 2024; Tong et al., 2024).

In a separate line of research, we explored how cells generate rhythmic contractile patterns. We found that pulses of actomyosin activity, driven by the GTPase Rho in mitotic cells, display features of chaotic behavior (Tong et al., Cell Reports 2023). This behavior is regulated by coupling phosphoinositide metabolism with nonvesicular lipid transfer through coupling two fast-slow oscillator cycles, a mathematical feature important for period doubling and intermediates towards deterministic chaos.

Our recent work has shown that these waves act as mechanosensitive, stimulus-responsive platforms that coordinate membrane trafficking, nonvesicular lipid transfer, cytoskeletal remodeling, and biochemical signaling. But is it possible to reduce this apparent complexity? We believe the answer is yes.

Read more in the page of Information Processing and Chaos.

1. Wu, Min*; Wu, Xudong; De Camilli, Pietro*. Calcium Oscillations-Coupled Conversion of Actin Travelling Waves to Standing Oscillations. Proc Natl Acad Sci U S A. 2013 22;110(4):1339-44. (* co-corresponding authors)
2. Wu, Zhanghan †; Su, Maohan †; Tong, Cheesan; Wu, Min*; Liu, Jian*. Membrane shape-mediated wave propagation of cortical protein dynamics. Nat. Comm. 2018, 9 (1), 136. (†co-first authors; * co-corresponding authors)
3. Su, Maohan; Zhuang Yinyin; Miao Xinwen; Zeng Yongpeng; Gao Weibo; Zhao Wenting*, Wu, Min*. Comparative study of curvature sensing mediated by F-BAR domain and an intrinsically disordered region of FBP17. ISCIENCE 2020, 23(11):101712. (* co-corresponding authors)
4. Tong, Cheesan; Xǔ, X. J.; Wu, Min*. Periodicity, Mixed-Mode Oscillations, and Multiple Timescale in a Phosphoinositide-Rho GTPase Network. Cell Rep. 2023, 42(8):112857.
5. Chua, X. L. et al. Competition and synergy of Arp2/3 and formins in nucleating actin waves. Cell Rep. 2024, 43, 114423.
6. Tong, Cheesan; Su, Maohan; Sun, He; Chua, Xiang Le; Guo, Su; Ravinraj S/O Ramaraj; Ong, Nicole Wen Pei; Lee, Ann Gie; Miao, Yansong; Wu, Min*; Collective dynamics of actin and microtubule and its crosstalk mediated by FHDC1. Front. Cell Dev. Biol. 2024, 11, 1261117.

Review

1. Yang, Yang; Wu, Min*. Rhythmicity and Waves in the Cortex of Single Cells. Phil. Trans. R. Soc. B. 2018, 373(1747).
2. Wu, Min*; Liu, Jian. Mechanobiology in Cortical Waves and Oscillations. Curr. Opin. Cell Biol. 2021, 68, 45–54.