Growth kinetics and power laws indicate distinct mechanisms of cell-cell interactions in the aggregation process

Cellular aggregation is a complex process orchestrated by various kinds of interactions depending on its environments. Different interactions give rise to different pathways of cellular rearrangement and the development of specialized tissues. To distinguish the underlying mechanisms, in this theoretical work, we investigate the spontaneous emergence of tissue patterns from an ensemble of single cells on a substrate following three leading pathways of cell-cell interactions, namely, direct cell adhesion contacts, matrix mediated mechanical interaction, and chemical signalling. Our analysis shows that the growth kinetics of the aggregation process is distinctly different for each pathway and bears the signature of the specific cell-cell interactions. Interestingly, we find that the average domain size and the mass of the clusters exhibit a power law growth in time under certain interaction mechanisms hitherto unexplored. Further, as observed in experiments, the cluster size distribution can be characterized by stretched exponential functions showing distinct cellular organization processes.

Articulating Fragrant Agarwood Formation as an Outcome of the Interaction between the Insect Zeuzera conferta and Aquilaria trees – A Review

Agarwood is the resinous infected wood obtained from Aquilaria species, which is a highly priced product in the flavour and fragrance market. Its formation is a complex process of interaction between the plant, insect, and microorganisms. Multiple studies concerning the interaction of microorganisms with the Aquilaria tree have been reported. However, the significant interaction between the insect Zeuzera conferta Walker (Lepidoptera: Cossidae) with Aquilaria has been overlooked, and only exiguous studies have been accomplished. Considering the dearth of available literature on this interesting phenomenon a review has been attempted. The taxonomical and morphological descriptions proffered by researchers and the insect life cycle are discussed. The review lays emphasis on the chemical ecology of the interaction between Z. conferta, Aquilaria and associating microorganisms as a possible continuum operating in the form of complex chemical signalling via release and sensing of Volatile Organic Compounds (VOCs), Herbivore Induced Plant Volatiles (HIPVs) and Microbial Volatile Organic Compounds (MVOCs). The review also scrutinizes the future perspectives of understanding the interaction in devising suitable management strategies to prevent uncontrolled infestation and, simultaneously, develop artificial rearing technology for the insect Z. conferta as a strategy for ensuring sustainable livelihood of farmers dependent on agarwood production.

Optineurin links Hace1-dependent Rac ubiquitylation to integrin-mediated mechanotransduction to control bacterial invasion and cell division

Extracellular matrix (ECM) elasticity is perceived by cells via focal adhesion structures, which transduce mechanical cues into chemical signalling to conform cell behaviour. Although the contribution of ECM compliance to the control of cell migration or division has been extensively studied, little has been reported regarding infectious processes. We have studied how mechanical properties of the ECM impact invasion of cells by the extraintestinal Escherichia coli pathogen UTI89. We show that UTI89 takes advantage, via its CNF1 toxin, of integrin mechanoactivation to trigger its invasion into cells. We identified OPTN as a protein regulated by ECM stiffness whose function is required for bacterial invasion and integrin mechanical coupling and for stimulation of HACE1 E3 ligase activity towards the Rac1 GTPase. We showed that OPTN knockdown cells display enhanced Rac1 activation, strong mechanochemical adhesion signalling and increased cyclin D1 translation, together with enhanced cell proliferation independent of ECM stiffness. Despite such features, OPTN knockdown cells displayed defective traction force buildup associated with limited cellular invasion by UTI89. Together, our data indicate that OPTN, through a new role in mechanobiology, supports CNF1-producing uropathogenic E. coli invasion and links HACE1-mediated ubiquitylation of Rac1 to ECM mechanical properties and integrin mechanotransduction.

Biological Roles of Lipocalins in Chemical Communication, Reproduction, and Regulation of Microbiota

Major evolutionary transitions were always accompanied by genetic remodelling of phenotypic traits. For example, the vertebrate transition from water to land was accompanied by rapid evolution of olfactory receptors and by the expansion of genes encoding lipocalins, which – due to their transporting functions – represent an important interface between the external and internal organic world of an individual and also within an individual. Similarly, some lipocalin genes were lost along other genes when this transition went in the opposite direction leading, for example, to cetaceans. In terrestrial vertebrates, lipocalins are involved in the transport of lipophilic substances, chemical signalling, odour reception, antimicrobial defence and background odour clearance during ventilation. Many ancestral lipocalins have clear physiological functions across the vertebrate taxa while many other have – due to pleiotropic effects of their genes – multiple or complementary functions within the body homeostasis and development. The aim of this review is to deconstruct the physiological functions of lipocalins in light of current OMICs techniques. We concentrated on major findings in the house mouse in comparison to other model taxa (e.g., voles, humans, and birds) in which all or most coding genes within their genomes were repeatedly sequenced and their annotations are sufficiently informative.

Connexin 43 and Connexin 26 Involvement in the Ponatinib-Induced Cardiomyopathy: Sex-Related Differences in a Murine Model

Cardiac connexins (Cxs) are proteins responsible for proper heart function. They form gap junctions that mediate electrical and chemical signalling throughout the cardiac system, and thus enable a synchronized contraction. Connexins can also individually participate in many signal transduction pathways, interacting with intracellular proteins at various cellular compartments. Altered connexin expression and localization have been described in diseased myocardium and the aim of this study is to assess the involvement of Cx43, Cx26, and some related molecules in ponatinib-induced cardiac toxicity. Ponatinib is a new multi-tyrosine kinase inhibitor that has been successfully used against human malignancies, but its cardiotoxicity remains worrisome. Therefore, understanding its signaling mechanism is important to adopt potential anti cardiac damage strategies. Our experiments were performed on hearts from male and female mice treated with ponatinib and with ponatinib plus siRNA-Notch1 by using immunofluorescence, Western blotting, and proteomic analyses. The altered cardiac function and the change in Cxs expression observed in mice after ponatinib treatment, were results dependent on the Notch1 pathway and sex. Females showed a lower susceptibility to ponatinib than males. The downmodulation of cardiac Cx43, Cx26 and miR-122, high pS368-Cx43 phosphorylation, cell viability and survival activation could represent some of the female adaptative/compensatory reactions to ponatinib cardiotoxicity.

A modular microfluidic bioreactor to investigate plant cell–cell interactions

Plants produce a wide variety of secondary metabolites, which often are of interest to pharmaceutical and nutraceutical industry. Plant-cell cultures allow producing these metabolites in a standardised manner, independently from various biotic and abiotic factors difficult to control during conventional cultivation. However, plant-cell fermentation proves to be very difficult, since these chemically complex compounds often result from the interaction of different biosynthetic pathways operating in different cell types. To simulate such interactions in cultured cells is a challenge. Here, we present a microfluidic bioreactor for plant-cell cultivation to mimic the cell–cell interactions occurring in real plant tissues. In a modular set-up of several microfluidic bioreactors, different cell types can connect through a flow that transports signals or metabolites from module to module. The fabrication of the chip includes hot embossing of a polycarbonate housing and subsequent integration of a porous membrane and in-plane tube fittings in a two-step ultrasonic welding process. The resulting microfluidic chip is biocompatible and transparent. Simulation of mass transfer for the nutrient sucrose predicts a sufficient nutrient supply through the membrane. We demonstrate the potential of this chip for plant cell biology in three proof-of-concept applications. First, we use the chip to show that tobacco BY-2 cells in suspension divide depending on a “quorum-sensing factor” secreted by proliferating cells. Second, we show that a combination of two Catharanthus roseus cell strains with complementary metabolic potency allows obtaining vindoline, a precursor of the anti-tumour compound vincristine. Third, we extend the approach to operationalise secretion of phytotoxins by the fungus Neofusicoccum parvum as a step towards systems to screen for interorganismal chemical signalling.

Volatile scent chemicals in the urine of the red fox, Vulpes vulpes

The red fox is a highly adaptable mammal that has established itself world-wide in many different environments. Contributing to its success is a social structure based on chemical signalling between individuals. Urine scent marking behaviour has long been known in foxes, but there has not been a recent study of the chemical composition of fox urine. We have used solid-phase microextraction and gas chromatography-mass spectrometry to analyze the urinary volatiles in 15 free-ranging wild foxes (2 female) living in farmlands and bush in Victoria, Australia. Foxes here are routinely culled as feral pests, and the urine was collected by bladder puncture soon after death. Compounds were identified from their mass spectra and Kovats retention indices. There were 53 possible endogenous scent compounds, 10 plant-derived compounds and 5 anthropogenic xenobiotics. Among the plant chemicals were several aromatic apocarotenoids previously found in greater abundance in the fox tail gland. They reflect the dietary consumption of carotenoids, essential for optimal health. One third of all the endogenous volatiles were sulfur compounds, a highly odiferous group which included thiols, methylsulfides and polysulfides. Five of the sulfur compounds (3-isopentenyl thiol, 1- and 2-phenylethyl methyl sulfide, octanethiol and benzyl methyl sulfide) have only been found in foxes, and four others (isopentyl methyl sulfide, 3-isopentenyl methyl sulfide, and 1- and 2-phenylethane thiol) only in some canid, mink and skunk species. This indicates that they are not normal mammalian metabolites and have evolved to serve a specific role. This role is for defence in musteloids and most likely for chemical communication in canids. The total production of sulfur compounds varied greatly between foxes (median 1.2, range 0.4–32.3 μg ‘acetophenone equivalents’/mg creatinine) as did the relative abundance of different chemical types. The urinary scent chemistry may represent a highly evolved system of semiochemicals for communication between foxes.

Pulsatile contractions and pattern formation in excitable active gels

The actin cortex is an active adaptive material, embedded with complex regulatory networks that can sense, generate and transmit mechanical forces. The cortex can exhibit a wide range of dynamic behaviours, from generating pulsatory contractions and traveling waves to forming highly organised structures such as ordered fibers, contractile rings and networks that must adapt to the local cellular environment. Despite the progress in characterising the biochemical and mechanical components of the actin cortex, our quantitative understanding of the emergent dynamics of this mechanochemical system is limited. Here we develop a mathematical model for the RhoA signalling network, the upstream regulator for actomyosin assembly and contractility, coupled to an active polymer gel, to investigate how the interplay between chemical signalling and mechanical forces govern the propagation of contractile stresses and patterns in the cortex. We demonstrate that mechanical feedback in the excitable RhoA system, through dilution and concentration of chemicals, acts to destabilise homogeneous states and robustly generate pulsatile contractions. While moderate active stresses generate spatial propagation of contraction pulses, higher active stresses assemble localised contractile structures. Moreover, mechanochemical feedback induces memory in the active gel, enabling long-range propagation of transient local signals.