Biology subjects

Wu, C.-X.

Publications and source records attributed to Wu, C.-X..

5 recordsLinked to original sources

bioRxiv2024

Determination of Gaussian curvature modulus and spontaneous curvature via membrane buckling

The elastic properties of membranes are typically characterized by a few phenomenological parameters, including bending and Gaussian curvature moduli measuring the membrane rigidity against its deformation and topological change, as well as spontaneous curvature arising from the asymmetry between the two leaflets in the lipid bilayers. Though tether-based and fluctuation-based experiments are commonly utilized to measure the bending modulus, measuring the Gaussian curvature modulus and the spontaneous curvature of the membrane is considered to be much more difficult. In this paper, we study the buckling process of a circular membrane with nonzero spontaneous curvature under compressive stresses. It is found that when the stress exceeds a critical value, the circular membrane will transform from a spherical cap to a buckled shape, with its buckling degree enhanced with the increase of stress until its base is constricted to almost zero. As the stress-strain relationship of the buckled membrane strongly depends on the Gaussian curvature modulus and the spontaneous curvature,we therefore propose a method to determine the Gaussian curvature modulus and the spontaneous curvature simultaneously by measuring its stress-strain relationship during a buckling process.

biophysics↗

bioRxiv2023

Membrane buckling and the determination of Gaussian curvature modulus

Biological membranes are able to exhibit various morphology due to the fluidity of the lipid molecules within the monolayers. The shape transformation of membranes has been well described by the classical Helfrich theory, which consists only a few phenomenological parameters, including the mean and the Gaussian curvature modulus. Though various methods have been proposed to measure the mean curvature modulus, determination of the Gaussian curvature modulus remains difficult both in experiments and in simulation. In this paper we study the buckling process of a rectangular membrane and a circular membrane subject to compressive stresses and under different boundary conditions. We find that the buckling of a rectangular membrane takes place continuously, while the buckling of a circular membrane can be discontinous depending on the boundary conditions. Furthermore, our results show that the stress-strain relationship of a buckled circular membrane can be used to effectively determine the Gaussian curvature modulus.

biophysics↗

bioRxiv2023

Pressure-driven membrane inflation through nanopores on the cell wall

Walled cells, such as plants and fungi, compose an important part of the model systems in biology. The cell wall primarily functions to prevent the cell from over-expansion when exposed to water, and is a porous material distributed with nanosized pores on it. In this paper, we study the deformation of a membrane patch by an osmotic pressure through a nanopore on the cell wall. We find that there exists a critical pore size beyond which the membrane cannot stand against the pressure and would inflate out through the pore. The critical pore size scales exponentially with the membrane tension and the spontaneous curvature, and exhibits a power law dependence on the osmotic pressure. Our results also show that the liquid membrane expansion by pressure is mechanically different from the solid balloon expansion, and predict that the bending rigidity of the membrane in walled cells should be larger than that of the mammalian cells so as to prevent inflation through the pores on the cell wall.

biophysics↗

bioRxiv2021

SARS-CoV-2-Triggered Mast Cell Rapid Degranulation Induces Alveolar Epithelial Inflammation and Lung Injury

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/449680v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@899996org.highwire.dtl.DTLVardef@1c26c0eorg.highwire.dtl.DTLVardef@1442cdcorg.highwire.dtl.DTLVardef@dd4204_HPS_FORMAT_FIGEXP M_FIG C_FIG In BriefSARS-CoV-2 triggers an immediate mast cell (MC) degranulation, which initiates the alveolar epithelial inflammation and disrupts the tight junction. MC stabilizers that block degranulation reduce virus-induced lung inflammation and injury. HighlightsO_LIThe binding of RBD of Spike protein of SARS-CoV-2-to ACE2 receptor protein triggers an immediate MC degranulation C_LIO_LIMC degranulation induces transcriptomic changes include an upregulated inflammatory signaling and a downregulated cell-junction signaling C_LIO_LIMC degranulation leads to alveolar epithelial inflammation and disruption of tight junctions C_LIO_LIMC stabilizer that inhibits degranulation reduces SARS-CoV-2-induced lung inflammation and injury in vivo C_LI

microbiology↗

bioRxiv2019

A revised 1.6 Å structure of the GTPase domain of the Parkinson’s disease-associated protein LRRK2 provides insights into mechanisms

Leucine-rich repeat kinase 2 (LRRK2) is a large 286 kDa multi-domain protein whose mutation is a common cause of Parkinsons disease (PD). One of the common sites of familial PD-associated mutations occurs at residue Arg-1441 in the GTPase domain of LRRK2. Previously, we reported that the PD-associated mutation R1441H impairs the catalytic activity of the GTPase domain thereby traps it in a persistently \"on\" state. More recently, we reported that the GTPase domain of LRRK2 exists in a dynamic dimer-monomer equilibrium where GTP binding shifts it to the monomeric conformation while GDP binding shifts it back to the dimeric state. We also reported that all of the PD-associated mutations at Arg-1441, including R1441H, R1441C, and R1441G, impair the nucleotide-dependent dimer-monomer conformational dynamics of the GTPase domain. However, the mechanism of this nucleotide-dependent conformational dynamics and how it is impaired by the mutations at residue Arg-1441 remained unclear. Here, we report a 1.6 [A] crystal structure of the GTPase domain of LRRK2. Our structure has revealed a dynamic switch region that can be differentially regulated by GTP and GDP binding. This nucleotide-dependent regulation is impaired when residue Arg-1441 is substituted with the PD-associated mutations due to the loss of its exquisite interactions consisting of two hydrogen bonds and a {pi}-stacking interaction at the dimer interface.\n\nSignificance StatementMutations in LRRK2 are associated with familial Parkinsons disease, so understanding its mechanism of actions and how they are changed by the disease-associated mutations is important for developing therapeutic strategies. This paper describes an atomic structure of the G-domain of LRRK2 revealing that the conformational dynamics of the switch regions are potentially important for its normal function. It further shows that a disease-associated mutation could lock the G domain in a persistently active-like conformation, thus perturbing its normal function.

biochemistry↗