Transitions between cooperative and crowding-dominated collective motion in non-jammed MDCK monolayers.

Transitions between solid-like and fluid-like states in living tissues have been found in steps of embryonic development and in stages of disease progression. Our current understanding of these transitions has been guided by experimental and theoretical investigations focused on how motion becomes arrested with increased mechanical coupling between cells, typically as a function of packing density or cell cohesiveness. However, cells actively respond to externally applied forces by contracting after a time delay, so it is possible that at some packing densities or levels of cell cohesiveness, mechanical coupling stimulates cell motion instead of suppressing it.

Discovery of 22(S)-23-phenyl-24-norchol-5-en-3β,22-diol (PFM046) as the first-in-class, steroidal, non-sulfated Liver X Receptor antagonist with anticancer activity.

A plethora of studies have demonstrated the crucial role played by Liver X Receptors (LXRs) in cancer. However, whether LXRs activation results in pro-versus anti-tumor effects is still matter of debate. Recently, we have reported the ability of 22(S)-hydroxycholesterol-3-sulfate (PFM037) to antagonize LXRα activity, and, at the same time, its capability to improve in-vivo anti-tumor immune responses.

Determining Rates of Molecular Secretion from Supernatant Concentration Measurements in a 3D-Bioprinted Human Liver Tissue Model.

The secretion rate of albumin is a key indicator of function in liver tissue models used for hepatotoxicity and pharmacokinetic testing. However, it is not generally clear how to determine molecular secretion rates from measurements of the molecular concentration in supernatant media. Here, we develop computational and analytical models of molecular transport in an experimental system that enable determination of albumin secretion rates based on measurements of albumin concentration in supernatant media.

Collagen Networks under Indentation and Compression Behave Like Cellular Solids.

Simple synthetic and natural hydrogels can be formulated to have elastic moduli that match biological tissues, leading to their widespread application as model systems for tissue engineering, medical device development, and drug delivery vehicles. However, two different hydrogels having the same elastic modulus but differing in microstructure or nanostructure can exhibit drastically different mechanical responses, including their poroelasticity, lubricity, and load bearing capabilities. Here, we investigate the mechanical response of collagen-1 networks to local and bulk compressive loads.

Side-Chain Chemistry Governs Hierarchical Order of Charge-Complementary β-sheet Peptide Coassemblies.

Self-assembly of proteinaceous biomolecules into functional materials with ordered structures that span length scales is common in nature yet remains a challenge with designer peptides under ambient conditions. This report demonstrates how charged side-chain chemistry affects the hierarchical co-assembly of a family of charge-complementary β-sheet-forming peptide pairs known as CATCH(X+/Y-) at physiologic pH and ionic strength in water. In a concentration-dependent manner, the CATCH(6K+) (Ac-KQKFKFKFKQK-Am) and CATCH(6D-) (Ac-DQDFDFDFDQD-Am) pair formed either β-sheet-rich microspheres or β-sheet-rich gels with a micron-scale plate-like morphology, which were not observed with other CATCH(X+/Y-) pairs.

A silicone-based support material eliminates interfacial instabilities in 3D silicone printing.

Among the diverse areas of 3D printing, high-quality silicone printing is one of the least available and most restrictive. However, silicone-based components are integral to numerous advanced technologies and everyday consumer products. We developed a silicone 3D printing technique that produces precise, accurate, strong, and functional structures made from several commercially available silicone formulations.

Injectable Microporous Annealed Particle Hydrogel Based on Guest-Host-Interlinked Polyethylene Glycol Maleimide Microgels.

Microporous annealed particle (MAP) hydrogels have emerged as a versatile biomaterial platform for regenerative medicine. MAP hydrogels have been used for the delivery of cells and organoids but often require annealing post injection by an external source. We engineered an injectable, self-annealing MAP hydrogel with reversible interparticle linkages based on guest-host functionalized polyethylene glycol maleimide (PEG-MAL) microgels.

Cellular micromasonry: biofabrication with single cell precision.

In many tissues, cell type varies over single-cell length-scales, creating detailed heterogeneities fundamental to physiological function. To gain understanding of the relationship between tissue function and detailed structure, and eventually to engineer structurally and physiologically accurate tissues, we need the ability to assemble 3D cellular structures having the level of detail found in living tissue. Here we introduce a method of 3D cell assembly having a level of precision finer than the single-cell scale.

Leveraging ultra-low interfacial tension and liquid-liquid phase separation in embedded 3D bioprinting.

Many recently developed 3D bioprinting strategies operate by extruding aqueous biopolymer solutions directly into a variety of different support materials constituted from swollen, solvated, aqueous, polymer assemblies. In developing these 3D printing methods and materials, great care is often taken to tune the rheological behaviors of both inks and 3D support media. By contrast, much less attention has been given to the physics of the interfaces created when structuring one polymer phase into another in embedded 3D printing applications.

Assessment of Optimal Conditions for Marine Invertebrate Cell-Mediated Mineralization of Organic Matrices.

Cellular strategies and regulation of their crystallization mechanisms are essential to the formation of biominerals, and harnessing these strategies will be important for the future creation of novel non-native biominerals that recapitulate the impressive properties biominerals possess. Harnessing these biosynthetic strategies requires an understanding of the interplay between insoluble organic matrices, mineral precursors, and soluble organic and inorganic additives. Our long-range goal is to use a sea anemone model system () to examine the role of intrinsically disordered proteins (IDPs) found in native biomineral systems.

Embedded 3D Printing in Self-Healing Annealable Composites for Precise Patterning of Functionally Mature Human Neural Constructs.

Human in vitro models of neural tissue with tunable microenvironment and defined spatial arrangement are needed to facilitate studies of brain development and disease. Towards this end, embedded printing inside granular gels holds great promise as it allows precise patterning of extremely soft tissue constructs. However, granular printing support formulations are restricted to only a handful of materials.

Microindentation of cartilage before and after articular loading in a bioreactor: assessment of length-scale dependency using two analysis methods.

Background: Microindentation is a technique with high sensitivity and spatial resolution, allowing for measurements at small-scale indentation depths. Various methods of indentation analysis to determine output properties exist.

Objective: Here, the Oliver-Pharr Method and Hertzian Method were compared for stiffness analyses of articular cartilage at varying length-scales before and after bioreactor loading.

Mechanical Characterization of Glandular Acini Using a Micro-indentation Instrument.

The linker of nucleoskeleton and cytoskeleton (LINC) complex is responsible for tethering the nucleus to the cytoskeleton, providing a pathway for the cell's nucleus to sense mechanical signals from the environment. Recently, we explored the role of the LINC complex in the development of glandular epithelial acini, such as those found in kidneys, breasts, and other organs. Acini developed with disrupted LINC complexes exhibited a loss of structural integrity, including filling of the lumen structures.

Capillary forces drive buckling, plastic deformation, and break-up of 3D printed beams.

Capillary forces acting at the interfaces of soft materials lead to deformations over the scale of the elastocapillary length. When surface stresses exceed a material's yield stress, a plastocapillary effect is expected to arise, resulting in yielding and plastic deformation. Here, we explore the interfacial instabilities of 3D-printed fluid and elastic beams embedded within viscoelastic fluids and elastic solid support materials.

Guest-host interlinked PEG-MAL granular hydrogels as an engineered cellular microenvironment.

We report the development of a polyethylene glycol (PEG) hydrogel scaffold that provides the advantages of conventional bulk PEG hydrogels for engineering cellular microenvironments and allows for rapid cell migration. PEG microgels were used to assemble a densely packed granular system with an intrinsic interstitium-like negative space. In this material, guest-host molecular interactions provide reversible non-covalent linkages between discrete PEG microgel particles to form a cohesive bulk material.

Cryopreservation impairs 3-D migration and cytotoxicity of natural killer cells.

Natural killer (NK) cells are important effector cells in the immune response to cancer. Clinical trials on adoptively transferred NK cells in patients with solid tumors, however, have thus far been unsuccessful. As NK cells need to pass stringent safety evaluation tests before clinical use, the cells are cryopreserved to bridge the necessary evaluation time.

Correction: 3D aggregation of cells in packed microgel media.

Correction for '3D aggregation of cells in packed microgel media' by Cameron D. Morley et al., Soft Matter, 2020, DOI: 10.

3D aggregation of cells in packed microgel media.

In both natural and applied contexts, investigating cell self-assembly and aggregation within controlled 3D environments leads to improved understanding of how structured cell assemblies emerge, what determines their shapes and sizes, and whether their structural features are stable. However, the inherent limits of using solid scaffolding or liquid spheroid culture for this purpose restrict experimental freedom in studies of cell self-assembly. Here we investigate multi-cellular self-assembly using a 3D culture medium made from packed microgels as a bridge between the extremes of solid scaffolds and liquid culture.

Deep learning based classification of solid lipid-poor contrast enhancing renal masses using contrast enhanced CT.

Objective: Establish a workflow that utilizes convolutional neural nets (CNN) to classify solid, lipid-poor, contrast enhancing renal masses using multiphase contrast enhanced CT (CECT) images and to assess the performance of the resulting network.

Methods: In this institutional review board approved study of 143 patients with predominantly solid, lipid-poor, contrast enhancing renal lesions (46 benign and 97 malignant), patients with a pre-operative multiphase CECT of the abdomen and pelvis obtained between June 2009 and June 2015 were retrospectively queried. Benign renal masses included oncocytoma and lipid-poor angiomyolipoma and the malignant group included clear cell, papillary, and chromophobe carcinomas.

Regeneration in the ctenophore Mnemiopsis leidyi occurs in the absence of a blastema, requires cell division, and is temporally separable from wound healing.

Background: The ability to regenerate is a widely distributed but highly variable trait among metazoans. A variety of modes of regeneration has been described for different organisms; however, many questions regarding the origin and evolution of these strategies remain unanswered. Most species of ctenophore (or "comb jellies"), a clade of marine animals that branch off at the base of the animal tree of life, possess an outstanding capacity to regenerate.

Anthracene-based mechanophores for compression-activated fluorescence in polymeric networks.

The recent attention given to functionalities that respond to mechanical force has led to a deeper understanding of force transduction and mechanical wear in polymeric materials. Furthermore, polymers have been carefully designed such that activation of "mechanophores" leads to productive outputs, such as material reinforcement or changes in optical properties. In this work, a crosslinker containing an anthracene-maleimide linkage was designed and used to prepare networks that display a fluorescence response when damaged.

Mechanical Stabilization of the Glandular Acinus by Linker of Nucleoskeleton and Cytoskeleton Complex.

The nucleoskeleton and cytoskeleton are important protein networks that govern cellular behavior and are connected together by the linker of nucleoskeleton and cytoskeleton (LINC) complex. Mutations in LINC complex components may be relevant to cancer, but how cell-level changes might translate into tissue-level malignancy is unclear. We used glandular epithelial cells in a three-dimensional culture model to investigate the effect of perturbations of the LINC complex on higher order cellular architecture.

Quantitative characterization of 3D bioprinted structural elements under cell generated forces.

With improving biofabrication technology, 3D bioprinted constructs increasingly resemble real tissues. However, the fundamental principles describing how cell-generated forces within these constructs drive deformations, mechanical instabilities, and structural failures have not been established, even for basic biofabricated building blocks. Here we investigate mechanical behaviours of 3D printed microbeams made from living cells and extracellular matrix, bioprinting these simple structural elements into a 3D culture medium made from packed microgels, creating a mechanically controlled environment that allows the beams to evolve under cell-generated forces.

Repair of nuclear ruptures requires barrier-to-autointegration factor.

Cell nuclei rupture following exposure to mechanical force and/or upon weakening of nuclear integrity, but nuclear ruptures are repairable. Barrier-to-autointegration factor (BAF), a small DNA-binding protein, rapidly localizes to nuclear ruptures; however, its role at these rupture sites is unknown. Here, we show that it is predominantly a nonphosphorylated cytoplasmic population of BAF that binds nuclear DNA to rapidly and transiently localize to the sites of nuclear rupture, resulting in BAF accumulation in the nucleus.

Jammed Polyelectrolyte Microgels for 3D Cell Culture Applications: Rheological Behavior with Added Salts.

The yielding and jamming behaviors of packed granular-scale microgels enable their use as a support medium for 3D printing stable shapes made from liquid phases; under low levels of applied stress, jammed microgel packs behave like elastic solids and provide support to spatially patterned fluid structures. When swollen in cell growth media, these microgels constitute a biomaterial for bioprinting and 3D cell culture applications. However, interactions between polyelectrolytes commonly used in microgels and multivalent ions present in cell growth media may lead to drastic and adverse changes in rheological behavior or cell performance.