Chemotactic smoothing of collective migration

Collective migration-the directed, coordinated motion of many self-propelled agents-is a fascinating emergent behavior exhibited by active matter with functional implications for biological systems. However, how migration can persist when a population is confronted with perturbations is poorly understood. Here, we address this gap in knowledge through studies of bacteria that migrate via directed motion, or chemotaxis, in response to a self-generated nutrient gradient. We find that bacterial populations autonomously smooth out large-scale perturbations in their overall morphology, enabling the cells to continue to migrate together. This smoothing process arises from spatial variations in the ability of cells to sense and respond to the local nutrient gradient-revealing a population-scale consequence of the manner in which individual cells transduce external signals. Altogether, our work provides insights to predict, and potentially control, the collective migration and morphology of cellular populations and diverse other forms of active matter. eLife digest Flocks of birds, schools of fish and herds of animals are all good examples of collective migration, where individuals co-ordinate their behavior to improve survival. This process also happens on a cellular level; for example, when bacteria consume a nutrient in their surroundings, they will collectively move to an area with a higher concentration of food via a process known as chemotaxis. Several studies have examined how disturbing collective migration can cause populations to fall apart. However, little is known about how groups withstand these interferences. To investigate, Bhattacharjee, Amchin, Alert et al. studied bacteria called Escherichia coli as they moved through a gel towards nutrients. The E. coli were injected into the gel using a three-dimensional printer, which deposited the bacteria into a wiggly shape that forces the cells apart, making it harder for them to move as a collective group. However, as the bacteria migrated through the gel, they smoothed out the line and gradually made it straighter so they could continue to travel together over longer distances. Computer simulations revealed that this smoothing process is achieved by differences in how the cells respond to local nutrient levels based on their position. Bacteria towards the front of the group are exposed to more nutrients, causing them to become oversaturated and respond less effectively to the nutrient gradient. As a result, they move more slowly, allowing the cells behind them to eventually catch-up. These findings reveal a general mechanism in which limitations in how individuals sense and respond to an external signal (in this case local nutrient concentrations) allows them to continue migrating together. This mechanism may apply to other systems that migrate via chemotaxis, as well as groups whose movement is directed by different external factors, such as temperature and light intensity

Chemotactic smoothing of collective migration

Collective migration -- the directed, coordinated motion of many self-propelled agents -- is a fascinating emergent behavior exhibited by active matter that has key functional implications for biological systems. Extensive studies have elucidated the different ways in which this phenomenon may arise. Nevertheless, how collective migration can persist when a population is confronted with perturbations, which inevitably arise in complex settings, is poorly understood. Here, by combining experiments and simulations, we describe a mechanism by which collectively migrating populations smooth out large-scale perturbations in their overall morphology, enabling their constituents to continue to migrate together. We focus on the canonical example of chemotactic migration of Escherichia coli, in which fronts of cells move via directed motion, or chemotaxis, in response to a self-generated nutrient gradient. We identify two distinct modes in which chemotaxis influences the morphology of the population: cells in different locations along a front migrate at different velocities due to spatial variations in (i) the local nutrient gradient and in (ii) the ability of cells to sense and respond to the local nutrient gradient. While the first mode is destabilizing, the second mode is stabilizing and dominates, ultimately driving smoothing of the overall population and enabling continued collective migration. This process is autonomous, arising without any external intervention; instead, it is a population-scale consequence of the manner in which individual cells transduce external signals. Our findings thus provide insights to predict, and potentially control, the collective migration and morphology of cell populations and diverse other forms of active matter

Clinically Relevant Interactions between Newer Antidepressants and Second-Generation Antipsychotics

INTRODUCTION: Combinations of newer antidepressants and second-generation antipsychotics (SGAs) are frequently used by clinicians. Pharmacokinetic drug interaction (PK DI) and poorly understood pharmacodynamic (PD) drug interaction (PD DI) can occur between them. AREAS COVERED: This paper comprehensively reviews PD DI and PK DI studies. EXPERT OPINION: More PK DI studies are needed to better establish dose correction factors after adding fluoxetine and paroxetine to aripiprazole, iloperidone and risperidone. Further PK DI studies and case reports are also needed to better establish the need for dose correction factors after adding i) fluoxetine to clozapine, lurasidone, quetiapine and olanzapine; ii) paroxetine to olanzapine; iii) fluvoxamine to asenapine, aripiprazole, iloperidone, lurasidone, olanzapine, quetiapine and risperidone; iv) high sertraline doses to aripiprazole, clozapine, iloperidone and risperidone: v) bupropion and duloxetine to aripiprazole, clozapine, iloperidone and risperidone; and vi) asenapine to paroxetine and venlafaxine. Possible beneficial PD DI effects occur after adding SGAs to newer antidepressants for treatment-resistant major depressive and obsessive-compulsive disorders. The lack of studies combining newer antidepressants and SGAs in psychotic depression is worrisome. PD DIs between newer antidepressants and SGAs may be more likely for mirtazapine and bupropion. Adding selective serotonin reuptake inhibitors and SGAs may increase QTc interval and may very rarely contribute to torsades de pointes