Multiflagellarity leads to the size-independent swimming speed of peritrichous bacteria.

To swim through a viscous fluid, a flagellated bacterium must overcome the fluid drag on its body by rotating a flagellum or a bundle of multiple flagella. Because the drag increases with the size of bacteria, it is expected theoretically that the swimming speed of a bacterium inversely correlates with its body length. Nevertheless, despite extensive research, the fundamental size-speed relation of flagellated bacteria remains unclear with different experiments reporting conflicting results. Here, by critically reviewing the existing evidence and synergizing our own experiments of large sample sizes, hydrodynamic modeling, and simulations, we demonstrate that the average swimming speed of Escherichia coli, a premier model of peritrichous bacteria, is independent of their body length. Our quantitative analysis shows that such a counterintuitive relation is the consequence of the collective flagellar dynamics dictated by the linear correlation between the body length and the number of flagella of bacteria. Notably, our study reveals how bacteria utilize the increasing number of flagella to regulate the flagellar motor load. The collective load sharing among multiple flagella results in a lower load on each flagellar motor and therefore faster flagellar rotation, which compensates for the higher fluid drag on the longer bodies of bacteria. Without this balancing mechanism, the swimming speed of monotrichous bacteria generically decreases with increasing body length, a feature limiting the size variation of the bacteria. Altogether, our study resolves a long-standing controversy over the size-speed relation of flagellated bacteria and provides insights into the functional benefit of multiflagellarity in bacteria.

Modeling of lophotrichous bacteria reveals key factors for swimming reorientation.

Lophotrichous bacteria swim through fluid by rotating their flagellar bundle extended collectively from one pole of the cell body. Cells experience modes of motility such as push, pull, and wrapping, accompanied by pauses of motor rotation in between. We present a mathematical model of a lophotrichous bacterium and investigate the hydrodynamic interaction of cells to understand their swimming mechanism. We classify the swimming modes which vary depending on the bending modulus of the hook and the magnitude of applied torques on the motor. Given the hook's bending modulus, we find that there exist corresponding critical thresholds of the magnitude of applied torques that separate wrapping from pull in CW motor rotation, and overwhirling from push in CCW motor rotation, respectively. We also investigate reoriented directions of cells in three-dimensional perspectives as the cell experiences different series of swimming modes. Our simulations show that the transition from a wrapping mode to a push mode and pauses in between are key factors to determine a new path and that the reoriented direction depends upon the start time and duration of the pauses. It is also shown that the wrapping mode may help a cell to escape from the region where the cell is trapped near a wall.

Role of extracellular matrix and microenvironment in regulation of tumor growth and LAR-mediated invasion in glioblastoma.

The cellular dispersion and therapeutic control of glioblastoma, the most aggressive type of primary brain cancer, depends critically on the migration patterns after surgery and intracellular responses of the individual cancer cells in response to external biochemical cues in the microenvironment. Recent studies have shown that miR-451 regulates downstream molecules including AMPK/CAB39/MARK and mTOR to determine the balance between rapid proliferation and invasion in response to metabolic stress in the harsh tumor microenvironment. Surgical removal of the main tumor is inevitably followed by recurrence of the tumor due to inaccessibility of dispersed tumor cells in normal brain tissue. In order to address this complex process of cell proliferation and invasion and its response to conventional treatment, we propose a mathematical model that analyzes the intracellular dynamics of the miR-451-AMPK- mTOR-cell cycle signaling pathway within a cell. The model identifies a key mechanism underlying the molecular switches between proliferative phase and migratory phase in response to metabolic stress in response to fluctuating glucose levels. We show how up- or down-regulation of components in these pathways affects the key cellular decision to infiltrate or proliferate in a complex microenvironment in the absence and presence of time delays and stochastic noise. Glycosylated chondroitin sulfate proteoglycans (CSPGs), a major component of the extracellular matrix (ECM) in the brain, contribute to the physical structure of the local brain microenvironment but also induce or inhibit glioma invasion by regulating the dynamics of the CSPG receptor LAR as well as the spatiotemporal activation status of resident astrocytes and tumor-associated microglia. Using a multi-scale mathematical model, we investigate a CSPG-induced switch between invasive and non-invasive tumors through the coordination of ECM-cell adhesion and dynamic changes in stromal cells. We show that the CSPG-rich microenvironment is associated with non-invasive tumor lesions through LAR-CSGAG binding while the absence of glycosylated CSPGs induce the critical glioma invasion. We illustrate how high molecular weight CSPGs can regulate the exodus of local reactive astrocytes from the main tumor lesion, leading to encapsulation of non-invasive tumor and inhibition of tumor invasion. These different CSPG conditions also change the spatial profiles of ramified and activated microglia. The complex distribution of CSPGs in the tumor microenvironment can determine the nonlinear invasion behaviors of glioma cells, which suggests the need for careful therapeutic strategies.

Modeling polymorphic transformation of rotating bacterial flagella in a viscous fluid.

The helical flagella that are attached to the cell body of bacteria such as Escherichia coli and Salmonella typhimurium allow the cell to swim in a fluid environment. These flagella are capable of polymorphic transformation in that they take on various helical shapes that differ in helical pitch, radius, and chirality. We present a mathematical model of a single flagellum described by Kirchhoff rod theory that is immersed in a fluid governed by Stokes equations. We perform numerical simulations to demonstrate two mechanisms by which polymorphic transformation can occur, as observed in experiments. First, we consider a flagellar filament attached to a rotary motor in which transformations are triggered by a reversal of the direction of motor rotation [L. Turner et al., J. Bacteriol. 182, 2793 (2000)10.1128/JB.182.10.2793-2801.2000]. We then consider a filament that is fixed on one end and immersed in an external fluid flow [H. Hotani, J. Mol. Biol. 156, 791 (1982)10.1016/0022-2836(82)90142-5]. The detailed dynamics of the helical flagellum interacting with a viscous fluid is discussed and comparisons with experimental and theoretical results are provided.

The role of myosin II in glioma invasion: A mathematical model.

Gliomas are malignant tumors that are commonly observed in primary brain cancer. Glioma cells migrate through a dense network of normal cells in microenvironment and spread long distances within brain. In this paper we present a two-dimensional multiscale model in which a glioma cell is surrounded by normal cells and its migration is controlled by cell-mechanical components in the microenvironment via the regulation of myosin II in response to chemoattractants. Our simulation results show that the myosin II plays a key role in the deformation of the cell nucleus as the glioma cell passes through the narrow intercellular space smaller than its nuclear diameter. We also demonstrate that the coordination of biochemical and mechanical components within the cell enables a glioma cell to take the mode of amoeboid migration. This study sheds lights on the understanding of glioma infiltration through the narrow intercellular spaces and may provide a potential approach for the development of anti-invasion strategies via the injection of chemoattractants for localization.

A Multiscale Model of Cardiovascular System Including an Immersed Whole Heart in the Cases of Normal and Ventricular Septal Defect (VSD).

A mathematical and computational model combining the heart and circulatory system has been developed to understand the hemodynamics of circulation under normal conditions and ventricular septal defect (VSD). The immersed boundary method has been introduced to describe the interaction between the moving two-dimensional heart and intracardiac blood flow. The whole-heart model is governed by the Navier-Stokes system; this system is combined with a multi-compartment model of circulation using pressure-flow relations and the linearity of the discretized Navier-Stokes system. We investigate the velocity field, flowmeters, and pressure-volume loop in both normal and VSD cases. Simulation results show qualitatively good agreements with others found in the literature. This model, combining the heart and circulation, is useful for understanding the complex, hemodynamic mechanisms involved in normal circulation and cardiac diseases.

Nonlinear dynamics of a rotating elastic rod in a viscous fluid.

The dynamics of an elastic rod in a viscous fluid at zero Reynolds number is investigated when the bottom end of the rod is tethered at a point in space and rotates at a prescribed angular frequency, while the other part of the rod freely moves through the fluid. A rotating elastic rod, which is intrinsically straight, exhibits three dynamical motions: twirling, overwhirling, and whirling. The first two motions are stable, whereas the last motion is unstable. The stability of dynamical motions is determined by material and geometrical properties of the rod, fluid properties, and the angular frequency of the rod. We employ the regularized Stokes flow to describe the fluid motion and the Kirchhoff rod model to describe the elastic rod. Our simulation results display subcritical Hopf bifurcation diagrams indicating the bistability region. We also investigate the whirling motion generated by the rotation of an intrinsically bent rod. It is observed that the angular frequency determines the handedness of the whirling rod and thus the flow direction and that there is a critical frequency which separates the positive (upward) flow at frequencies above it from the negative (downward) flow at frequencies below it.