Kismet/CHD7/CHD8 affects gut microbiota, mechanics, and the gut-brain axis in Drosophila melanogaster.

The gut microbiome affects brain and neuronal development and may contribute to the pathophysiology of neurodevelopmental disorders. However, it is unclear how risk genes associated with such disorders affect gut physiology in a manner that could impact microbial colonization and how the mechanical properties of the gut tissue might play a role in gut-brain bidirectional communication. To address this, we used Drosophila melanogaster with a null mutation in the gene kismet, an ortholog of chromodomain helicase DNA-binding protein (CHD) family members CHD7 and CHD8.

Stochastic ordering of complexoform protein assembly by genetic circuits.

Top-down proteomics has enabled the elucidation of heterogeneous protein complexes with different cofactors, post-translational modifications, and protein membership. This heterogeneity is believed to play a previously unknown role in cellular processes. The different molecular forms of a protein complex have come to be called "complex isoform" or "complexoform".

Minimizing Context Dependency of Gene Networks Using Artificial Cells.

The functioning of synthetic gene circuits depends on their local chemical context defined by the types and concentrations of biomolecules in the surrounding milieu that influences gene transcription and translation. This chemical-context dependence of synthetic gene circuits arises from significant yet unknown cross talk between engineered components, host cells, and environmental factors and has been a persistent challenge for synthetic biology. Here, we show that the sensitivity of synthetic gene networks to their extracellular chemical contexts can be minimized, and their designed functions rendered robust using artificial cells, which are synthetic biomolecular compartments engineered from the bottom-up using liposomes that encapsulate the gene networks.

Dynamic biomaterials: toward engineering autonomous feedback.

Dynamic biomaterials are biocompatible engineered systems capable of sensing and actively responding to their surrounding environment. They are of growing interest, both as models in basic research to understand complex cellular systems and in medical applications. Here, we review recent advances in nano-scale and micro-scale biomaterials, specifically artificial cells consisting of compartmentalized biochemical reactions and biologically compatible hydrogels.

Mechanics and dynamics of reconstituted cytoskeletal systems.

The intracellular cytoskeleton is an active dynamic network of filaments and associated binding proteins that control key cellular properties, such as cell shape and mechanics. Due to the inherent complexity of the cell, reconstituted model systems have been successfully employed to gain an understanding of the fundamental physics governing cytoskeletal processes. Here, we review recent advances and key aspects of these reconstituted systems.

Emergent properties of composite semiflexible biopolymer networks.

The semiflexible polymers filamentous actin (F-actin) and intermediate filaments (IF) both form complex networks within the cell, and together are key determinants of cellular stiffness. While the mechanics of F-actin networks together with stiff microtubules have been characterized, the interplay between F-actin and IF networks is largely unknown, necessitating the study of composite networks using mixtures of semiflexible biopolymers. We employ bulk rheology in a simplified in vitro system to uncover the fundamental mechanical interactions between networks of the 2 semiflexible polymers, F-actin and vimentin IF.

Mechanism of calponin stabilization of cross-linked actin networks.

The actin-binding protein calponin has been previously implicated in actin cytoskeletal regulation and is thought to act as an actin stabilizer, but the mechanism of its function is poorly understood. To investigate this underlying physical mechanism, we studied an in vitro model system of cross-linked actin using bulk rheology. Networks with basic calponin exhibited a delayed onset of strain stiffening (10.

The conformational state of actin filaments regulates branching by actin-related protein 2/3 (Arp2/3) complex.

Actin is a highly ubiquitous protein in eukaryotic cells that plays a crucial role in cell mechanics and motility. Cell motility is driven by assembling actin as polymerizing actin drives cell protrusions in a process closely involving a host of other actin-binding proteins, notably the actin-related protein 2/3 (Arp2/3) complex, which nucleates actin and forms branched filamentous structures. The Arp2/3 complex preferentially binds specific actin networks at the cell leading edge and forms branched filamentous structures, which drive cell protrusions, but the exact regulatory mechanism behind this process is not well understood.

Domain shapes, coarsening, and random patterns in ternary membranes.

A number of morphological and statistical aspects of domain formation in singly and doubly supported ternary membranes have been investigated. Such ternary membranes produce macroscopic phase separation in two fluid phases and are widely used as raft models. We find that membrane interactions with the support surface can have a critical influence on the domain shapes if measures are not taken to screen these interactions.