Research & Publications
Biological systems operate away from equilibrium but the applications of non-equilibrium dynamics in our current understanding of biology remain limited. The lab of Min Wu is fascinated by cortical oscillations and travelling waves that are regulated by interacting networks of phosphoinositide-metabolizing enzymes. The laboratory is currently investigating the mechanisms of these single cell pattern formation by high-resolution quantitative imaging, optogenetics and genome-editing. We aim to employ these spatial-temporal patterns as a conceptual framework to dissect fundamental cellular processes of cell growth, cell division, and cell size control.
Extensive Research Description
- During my postdoctoral training, I developed a cell-free system that reconstituted clathrin-dependent budding and dynamin-dependent fission reaction from plasma membrane sheets (Wu et al., Nature Cell Biology, 2010). We showed the cooperation of two classic forms of membrane trafficking intermediates: coated vesicles and membrane tubules.
- Using a combination of cell free reconstitution, single molecule imaging and cryo-electron tomography (in collaboration with Ruben Fernandez-Busnadiego lab), my lab discovered that dynamic turnover of clathrin during the assembly phase provides a proofreading checkpoint that is essential for cargo sorting in endocytosis (Chen Y et al., JCB 2019).
- We are the first to show that membrane-bending F-BAR proteins form travelling waves in cells (Wu et al., PNAS 2013). Two types of waves were observed (travelling waves and standing waves), and standing waves but not travelling waves are coupled with calcium oscillations. This unexpected observation was made in the course of investigating stimulation-dependent endocytosis, and it was motivated by findings from my cell-free reconstitution system.
- My lab later showed that these F-BAR waves are collective waves of endocytosis (Yang et al., Dev Cell 2017). These findings suggest individual budding events (namely formation of clathrin-coated pits) have non-autonomous effects that could positively feedback on each other, which lead to their partial synchronization.
- Cortical oscillations arise by delayed negative feedback mechanisms. My lab demonstrated that the negative feedbacks came from SHIP1-dependent degradation of Phosphatidylinositol (3,4,5)-trisphosphate, or PIP₃. Optogenetically tuning PI3K activation could modulate oscillation frequencies, indicating the activity level of PI3K is frequency-encoded (Xiong et al., Nature Chemical Biology 2016).
- In collaboration with Jian Liu group, we proposed a curvature-dependent mechanochemical feedback model to explain the ultrafast propagation speed which is 10-100 times faster than most reaction-diffusion type of cortical waves (Wu, Su et al., Nature Communication 2018). It can be thought of as a hybrid between trigger waves and phase waves.
- If changes in oscillation periods are not coupled with those of propagation speed, wavelengths of the cortical waves could be varied by simply changing oscillation frequency. We discovered that in mitotic cells, frequencies and wavelengths of mitotic waves scaled with cell size (Xiao et al., Dev Cell, 2017). In addition, cortical waves predict site of division in metaphase, much earlier than any known spindle-dependent mechanisms.
Cell size and growth
- Do cells know their sizes during cell growth? We developed a simple PDMS channel system to investigate cell size homeostasis (how a population of cells correct for size or growth variations and maintain their uniform size distribution). We found the presence of cryptic cell size checkpoints in mammalian cells but they were not the rate-limiting step for cells to enter S-phase. Instead, they grow a constant amount during G1-phase (“adder principle”, or size-independent net growth) and reach size homeostasis in a few generations (Varsano et al., Cell Reports 2017). Our work is the first to suggest this two-tier model in mammalian cells but it echos with the classic findings in budding and fission yeasts.
Organelle Biogenesis; Endocytosis; Growth; Homeostasis; Nonlinear Dynamics; Nanotechnology; Cell Shape; Wavelet Analysis; Phosphoinositide Phosphatases
- Cooperativity and competition in cortical actin wave formationSan Tong C, Su M, Chua X, Wu M. Cooperativity and competition in cortical actin wave formation Biophysical Journal 2022, 121: 17a. DOI: 10.1016/j.bpj.2021.11.2624.
- A kinetic view of clathrin assembly and endocytic cargo sortingWu M, Wu X. A kinetic view of clathrin assembly and endocytic cargo sorting Current Opinion In Cell Biology 2021, 71: 130-138. PMID: 33865229, DOI: 10.1016/j.ceb.2021.02.010.
- Curvature Sensing Mediated by F-BAR Domain and an Intrinsically Disordered Region of FBP17Su M, Zhuang Y, Zhao W, Wu M. Curvature Sensing Mediated by F-BAR Domain and an Intrinsically Disordered Region of FBP17 Biophysical Journal 2021, 120: 31a. DOI: 10.1016/j.bpj.2020.11.441.
- Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17Su M, Zhuang Y, Miao X, Zeng Y, Gao W, Zhao W, Wu M. Comparative Study of Curvature Sensing Mediated by F-BAR and an Intrinsically Disordered Region of FBP17 IScience 2020, 23: 101712. PMID: 33205024, PMCID: PMC7649350, DOI: 10.1016/j.isci.2020.101712.
- Mechanobiology in cortical waves and oscillationsWu M, Liu J. Mechanobiology in cortical waves and oscillations Current Opinion In Cell Biology 2020, 68: 45-54. PMID: 33039945, DOI: 10.1016/j.ceb.2020.08.017.
- Dynamic instability of clathrin assembly provides proofreading control for endocytosisChen Y, Yong J, Martínez-Sánchez A, Yang Y, Wu Y, De Camilli P, Fernández-Busnadiego R, Wu M. Dynamic instability of clathrin assembly provides proofreading control for endocytosis Journal Of Cell Biology 2019, 218: 3200-3211. PMID: 31451612, PMCID: PMC6781453, DOI: 10.1083/jcb.201804136.
- Deconstructing Actin WavesWu M. Deconstructing Actin Waves Structure 2019, 27: 1187-1189. PMID: 31390543, DOI: 10.1016/j.str.2019.07.010.
- Real-Time Monitoring of Clathrin Assembly Kinetics in a Reconstituted SystemYong J, Chen Y, Wu M. Real-Time Monitoring of Clathrin Assembly Kinetics in a Reconstituted System 2018, 1847: 177-187. PMID: 30129017, DOI: 10.1007/978-1-4939-8719-1_13.
- Rhythmicity and waves in the cortex of single cellsYang Y, Wu M. Rhythmicity and waves in the cortex of single cells Philosophical Transactions Of The Royal Society B Biological Sciences 2018, 373: 20170116. PMID: 29632268, PMCID: PMC5904302, DOI: 10.1098/rstb.2017.0116.
- Light, space, and time in cancer signalingMcPherson PS, Wu M. Light, space, and time in cancer signaling Molecular Biology Of The Cell 2018, 29: 688-688. PMID: 29535172, PMCID: PMC6003231, DOI: 10.1091/mbc.e17-11-0675.
- Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECsChen M, Qiu T, Wu J, Yang Y, Wright GD, Wu M, Ge R. Extracellular anti-angiogenic proteins augment an endosomal protein trafficking pathway to reach mitochondria and execute apoptosis in HUVECs Cell Death & Differentiation 2018, 25: 1905-1920. PMID: 29523874, PMCID: PMC6219483, DOI: 10.1038/s41418-018-0092-9.
- Membrane shape-mediated wave propagation of cortical protein dynamicsWu Z, Su M, Tong C, Wu M, Liu J. Membrane shape-mediated wave propagation of cortical protein dynamics Nature Communications 2018, 9: 136. PMID: 29321558, PMCID: PMC5762918, DOI: 10.1038/s41467-017-02469-1.
- Pulses and waves of contractilityWu M. Pulses and waves of contractility Journal Of Cell Biology 2017, 216: 3899-3901. PMID: 29138250, PMCID: PMC5716294, DOI: 10.1083/jcb.201710079.
- Mitotic Cortical Waves Predict Future Division Sites by Encoding Positional and Size InformationXiao S, Tong C, Yang Y, Wu M. Mitotic Cortical Waves Predict Future Division Sites by Encoding Positional and Size Information Developmental Cell 2017, 43: 493-506.e3. PMID: 29161593, DOI: 10.1016/j.devcel.2017.10.023.
- Clathrin Assembly Defines the Onset and Geometry of Cortical PatterningYang Y, Xiong D, Pipathsouk A, Weiner OD, Wu M. Clathrin Assembly Defines the Onset and Geometry of Cortical Patterning Developmental Cell 2017, 43: 507-521.e4. PMID: 29161594, PMCID: PMC5826602, DOI: 10.1016/j.devcel.2017.10.028.
- FFAR2‐FFAR3 receptor heteromerization modulates short‐chain fatty acid sensingAng Z, Xiong D, Wu M, Ding JL. FFAR2‐FFAR3 receptor heteromerization modulates short‐chain fatty acid sensing The FASEB Journal 2017, 32: 289-303. PMID: 28883043, PMCID: PMC5731126, DOI: 10.1096/fj.201700252rr.
- Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell ReshapingVarsano G, Wang Y, Wu M. Probing Mammalian Cell Size Homeostasis by Channel-Assisted Cell Reshaping Cell Reports 2017, 20: 397-410. PMID: 28700941, DOI: 10.1016/j.celrep.2017.06.057.
- Frequency and amplitude control of cortical oscillations by phosphoinositide wavesXiong D, Xiao S, Guo S, Lin Q, Nakatsu F, Wu M. Frequency and amplitude control of cortical oscillations by phosphoinositide waves Nature Chemical Biology 2016, 12: 159-166. PMID: 26751515, DOI: 10.1038/nchembio.2000.
- Shaping Developing Tissues with LightWu M. Shaping Developing Tissues with Light Developmental Cell 2015, 35: 533-534. PMID: 26651289, DOI: 10.1016/j.devcel.2015.11.020.
- Curvature-Generating Proteins and Subcellular Pattern FormationSu M, Tong C, Wu M. Curvature-Generating Proteins and Subcellular Pattern Formation Biophysical Journal 2015, 108: 244a. DOI: 10.1016/j.bpj.2014.11.1354.
- Intracellular Tracking of Single Native Molecules with Electroporation-Delivered Quantum DotsSun C, Cao Z, Wu M, Lu C. Intracellular Tracking of Single Native Molecules with Electroporation-Delivered Quantum Dots Analytical Chemistry 2014, 86: 11403-11409. PMID: 25341054, DOI: 10.1021/ac503363m.
- Multiarray cell stretching platform for high-magnification real-time imagingHuang Y, Nguyen NT, Lok KS, Lee PP, Su M, Wu M, Kocgozlu L, Ladoux B. Multiarray cell stretching platform for high-magnification real-time imaging Nanomedicine 2013, 8: 543-553. PMID: 23560406, DOI: 10.2217/nnm.13.45.
- Calcium oscillations-coupled conversion of actin travelling waves to standing oscillationsWu M, Wu X, De Camilli P. Calcium oscillations-coupled conversion of actin travelling waves to standing oscillations Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 1339-1344. PMID: 23297209, PMCID: PMC3557052, DOI: 10.1073/pnas.1221538110.
- Chapter 1 Supported Native Plasma Membranes as Platforms for the Reconstitution and Visualization of Endocytic Membrane BuddingWu M, De Camilli P. Chapter 1 Supported Native Plasma Membranes as Platforms for the Reconstitution and Visualization of Endocytic Membrane Budding 2012, 108: 1-18. PMID: 22325595, DOI: 10.1016/b978-0-12-386487-1.00001-8.
- Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free systemWu M, Huang B, Graham M, Raimondi A, Heuser JE, Zhuang X, De Camilli P. Coupling between clathrin-dependent endocytic budding and F-BAR-dependent tubulation in a cell-free system Nature Cell Biology 2010, 12: 902-908. PMID: 20729836, PMCID: PMC3338250, DOI: 10.1038/ncb2094.
- Three-dimensional Super-resolution Fluorescence Microscopy and Its Application to Clathrin Mediated EndocytosisHuang B, Wu M, Wang W, De Camilli P, Zhuang X. Three-dimensional Super-resolution Fluorescence Microscopy and Its Application to Clathrin Mediated Endocytosis Biophysical Journal 2009, 96: 16a. DOI: 10.1016/j.bpj.2008.12.987.
- Nanobiotechnology and Cell Biology: Micro- and Nanofabricated Surfaces to Investigate Receptor-Mediated SignalingTorres AJ, Wu M, Holowka D, Baird B. Nanobiotechnology and Cell Biology: Micro- and Nanofabricated Surfaces to Investigate Receptor-Mediated Signaling Annual Review Of Biophysics 2008, 37: 265-288. PMID: 18573082, DOI: 10.1146/annurev.biophys.36.040306.132651.
- Differential targeting of secretory lysosomes and recycling endosomes in mast cells revealed by patterned antigen arraysWu M, Baumgart T, Hammond S, Holowka D, Baird B. Differential targeting of secretory lysosomes and recycling endosomes in mast cells revealed by patterned antigen arrays Journal Of Cell Science 2007, 120: 3147-3154. PMID: 17698921, DOI: 10.1242/jcs.007260.
- Lipid segregation and IgE receptor signaling: A decade of progressHolowka D, Gosse J, Hammond A, Han X, Sengupta P, Smith N, Wagenknecht-Wiesner A, Wu M, Young R, Baird B. Lipid segregation and IgE receptor signaling: A decade of progress Biochimica Et Biophysica Acta 2005, 1746: 252-259. PMID: 16054713, DOI: 10.1016/j.bbamcr.2005.06.007.
- High Spatial Resolution Observation of Single-Molecule Dynamics in Living Cell MembranesEdel J, Wu M, Baird B, Craighead H. High Spatial Resolution Observation of Single-Molecule Dynamics in Living Cell Membranes Biophysical Journal 2005, 88: l43-l45. PMID: 15821167, PMCID: PMC1305672, DOI: 10.1529/biophysj.105.061937.
- Visualization of plasma membrane compartmentalization with patterned lipid bilayersWu M, Holowka D, Craighead HG, Baird B. Visualization of plasma membrane compartmentalization with patterned lipid bilayers Proceedings Of The National Academy Of Sciences Of The United States Of America 2004, 101: 13798-13803. PMID: 15356342, PMCID: PMC518836, DOI: 10.1073/pnas.0403835101.
- Mast Cell Activation on Patterned Lipid Bilayers of Subcellular Dimensions †Orth R, Wu M, Holowka D, Craighead H, Baird B. Mast Cell Activation on Patterned Lipid Bilayers of Subcellular Dimensions † Langmuir 2003, 19: 1599-1605. DOI: 10.1021/la026314c.
- Ionic liquids: applications in catalysisZhao D, Wu M, Kou Y, Min E. Ionic liquids: applications in catalysis Catalysis Today 2002, 74: 157-189. DOI: 10.1016/s0920-5861(01)00541-7.
- Nanoscale Patterning of Antigen on Silicon Substrate to Examine Mast Cell ActivationOrth R, Wu M, Clark T, Holowka D, Baird B, Craighead H. Nanoscale Patterning of Antigen on Silicon Substrate to Examine Mast Cell Activation MRS Advances 2002, 724: n4.3. DOI: 10.1557/proc-724-n4.3.
- Micro- and Nanofabricating Lipid Patterns Using a Polymer-Based Wet Lift-OffOrth R, Hafez I, Wu M, Ilic B, Baird B, Clark T, Craighead H. Micro- and Nanofabricating Lipid Patterns Using a Polymer-Based Wet Lift-Off MRS Advances 2001, 705: y7.18. DOI: 10.1557/proc-705-y7.18.