Decellularization and Enzymatic Digestion Methods to Enhance ECM Protein Detection via MALDI-MS Imaging.

Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) has been used to generate spatial maps of lipids, metabolites, peptides, proteins, and glycans in tissues; however, its use for mapping extracellular matrix (ECM) protein distributions is underexplored. ECM proteins play a major role in various pathological conditions, and changes in their spatial distributions affect the function and morphology of cells within tissues. ECM protein detection is challenging because they are large, insoluble, and undergo various post-translational modifications, such as glycosylation.

Sprayable inflammasome-inhibiting lipid nanorods in a polymeric scaffold for psoriasis therapy.

Localized delivery of inflammasome inhibitors in phagocytic macrophages could be promising for psoriasis treatment. The present work demonstrates the development of non-spherical lipid nanoparticles, mimicking pathogen-like shapes, consisting of an anti-inflammatory inflammasome inhibiting lipid (pyridoxine dipalmitate) as a trojan horse. The nanorods inhibit inflammasome by 3.

Needle-induced cavitation: A method to probe the local mechanics of brain tissue.

Traditional mechanical characterization of extremely soft tissues is challenging given difficulty extracting tissue, satisfying geometric requirements, keeping tissues hydrated, and securing the tissue in an apparatus without slippage. The heterogeneous nature and structural complexity of brain tissues on small length scales makes it especially difficult to characterize. Needle-induced cavitation (NIC) is a technique that overcomes these issues and can mechanically characterize brain tissues at precise, micrometer-scale locations.

Heterogeneity of brain extracellular matrix and astrocyte activation.

From the blood brain barrier to the synaptic space, astrocytes provide structural, metabolic, ionic, and extracellular matrix (ECM) support across the brain. Astrocytes include a vast array of subtypes, their phenotypes and functions varying both regionally and temporally. Astrocytes' metabolic and regulatory functions poise them to be quick and sensitive responders to injury and disease in the brain as revealed by single cell sequencing.

Outlook and opportunities for engineered environments of breast cancer dormancy.

Dormant, disseminated breast cancer cells resist treatment and may relapse into malignant metastases after decades of quiescence. Identifying how and why these dormant breast cancer cells are triggered into outgrowth is a key unsolved step in treating latent, metastatic breast cancer. However, our understanding of breast cancer dormancy in vivo is limited by technical challenges and ethical concerns with triggering the activation of dormant breast cancer.

Analysis of N- and O-linked site-specific glycosylation by ion mobility mass spectrometry: State of the art and future directions.

Glycosylation, the major post-translational modification of proteins, significantly increases the diversity of proteoforms. Glycans are involved in a variety of pivotal structural and functional roles of proteins, and changes in glycosylation are profoundly connected to the progression of numerous diseases. Mass spectrometry (MS) has emerged as the gold standard for glycan and glycopeptide analysis because of its high sensitivity and the wealth of fragmentation information that can be obtained.

Challenges and Opportunities Modeling the Dynamic Tumor Matrisome.

We need novel strategies to target the complexity of cancer and, particularly, of metastatic disease. As an example of this complexity, certain tissues are particularly hospitable environments for metastases, whereas others do not contain fertile microenvironments to support cancer cell growth. Continuing evidence that the extracellular matrix (ECM) of tissues is one of a host of factors necessary to support cancer cell growth at both primary and secondary tissue sites is emerging.

Engineering the endometrium.

Endometrial tissue is a dynamic environment that regenerates alongside the menstrual cycle and in response to sex hormones. This month in Med, Gnecco and colleagues present an innovative, synthetic model of endometrial environment that supports long-term cultures, simulates a 28-day menstrual cycle, and could be employed to investigate reproductive pathophysiology.

Tenascin-C Activation of Lung Fibroblasts in a 3D Synthetic Lung Extracellular Matrix Mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that match the ECM composition and biomechanics of the lung to study these cell-matrix interactions in vitro.

Modeling collective cell behavior in cancer: Perspectives from an interdisciplinary conversation.

Collective cell behavior contributes to all stages of cancer progression. Understanding how collective behavior emerges through cell-cell interactions and decision-making will advance our understanding of cancer biology and provide new therapeutic approaches. Here, we summarize an interdisciplinary discussion on multicellular behavior in cancer, draw lessons from other scientific disciplines, and identify future directions.

Tenascin-C activation of lung fibroblasts in a 3D synthetic lung extracellular matrix mimic.

The lung extracellular matrix (ECM) maintains the structural integrity of the tissue and regulates the phenotype and functions of resident fibroblasts. Lung-metastatic breast cancer alters these cell-ECM interactions, promoting fibroblast activation. There is a need for bio-instructive ECM models that contain the ECM composition and biomechanics of the lung to study these cell-matrix interactions .

Strain-Stiffening Hydrogels with Dynamic, Secondary Cross-Linking.

Hydrogels are water-swollen, typically soft networks useful as biomaterials and in other fields of biotechnology. Hydrogel networks capable of sensing and responding to external perturbations, such as light, temperature, pH, or force, are useful across a wide range of applications requiring on-demand cross-linking or dynamic changes. Thus far, although mechanophores have been described as strain-sensitive reactive groups, embedding this type of force-responsiveness into hydrogels is unproven.

Live Cell Lineage Tracing of Dormant Cancer Cells.

Breast cancer is a leading cause of global cancer-related deaths, and metastasis is the overwhelming culprit of poor patient prognosis. The most nefarious aspect of metastasis is dormancy, a prolonged period between primary tumor resection and relapse. Current therapies are insufficient at killing dormant cells; thus, they can remain quiescent in the body for decades until eventually undergoing a phenotypic switch, resulting in metastases that are more adaptable and drug resistant.

Agent-Based Models Help Interpret Patterns of Clinical Drug Resistance by Contextualizing Competition Between Distinct Drug Failure Modes.

Introduction: Modern targeted cancer therapies are carefully crafted small molecules. These exquisite technologies exhibit an astonishing diversity of observed failure modes (drug resistance mechanisms) in the clinic. This diversity is surprising because back of the envelope calculations and classic modeling results in evolutionary dynamics suggest that the diversity in the modes of clinical drug resistance should be considerably smaller than what is observed.

Systems approaches to uncovering the contribution of environment-mediated drug resistance.

Cancer drug response is heavily influenced by the extracellular matrix (ECM) environment. Despite a clear appreciation that the ECM influences cancer drug response and progression, a unified view of how, where, and when environment-mediated drug resistance contributes to cancer progression has not coalesced. Here, we survey some specific ways in which the ECM contributes to cancer resistance with a focus on how materials development can coincide with systems biology approaches to better understand and perturb this contribution.

Self-compassion training in palliative care during COVID-19: A pilot study.

Objectives: This pilot project replicated a self-compassion program to support health-care professionals in palliative care settings. We anticipated that undertaking this program would enhance participants' psychological well-being.

Methods: Participants were recruited by convenience sampling from palliative care services in an area of Melbourne, Australia.

Cavitation induced fracture of intact brain tissue.

Nonpenetrating traumatic brain injuries (TBIs) are linked to cavitation. The structural organization of the brain makes it particularly susceptible to tears and fractures from these cavitation events, but limitations in existing characterization methods make it difficult to understand the relationship between fracture and cavitation in this tissue. More broadly, fracture energy is an important, yet often overlooked, mechanical property of all soft tissues.

Materials-driven approaches to understand extrinsic drug resistance in cancer.

Metastatic cancer has a poor prognosis, because it is broadly disseminated and associated with both intrinsic and acquired drug resistance. Critical unmet needs in effectively killing drug resistant cancer cells include overcoming the drug desensitization characteristics of some metastatic cancers/lesions, and tailoring therapeutic regimens to both the tumor microenvironment and the genetic profiles of the resident cancer cells. Bioengineers and materials scientists are developing technologies to determine how metastatic sites exclude therapies, and how extracellular factors (including cells, proteins, metabolites, extracellular matrix, and abiotic factors) at metastatic sites significantly affect drug pharmacodynamics.

A poly(ethylene glycol) three-dimensional bone marrow hydrogel.

Three-dimensional (3D) hydrogels made from synthetic polymers have emerged as in vitro cell culture platforms capable of representing the extracellular geometry, modulus, and water content of tissues in a tunable fashion. Hydrogels made from these otherwise non-bioactive polymers can be decorated with short peptides derived from proteins naturally found in tissues to support cell viability and direct phenotype. We identified two key limitations that limit the ability of this class of materials to recapitulate real tissue.

Localized characterization of brain tissue mechanical properties by needle induced cavitation rheology and volume controlled cavity expansion.

Changes in the elastic properties of brain tissue have been correlated with injury, cancers, and neurodegenerative diseases. However, discrepancies in the reported elastic moduli of brain tissue are persistent, and spatial inhomogeneities complicate the interpretation of macroscale measurements such as rheology. Here we introduce needle induced cavitation rheology (NICR) and volume-controlled cavity expansion (VCCE) as facile methods to measure the apparent Young's modulus E of minimally manipulated brain tissue, at specific tissue locations and with sub-millimeter spatial resolution.