Spike Proteins of SARS-CoV-2 Induce Pathological Changes in Molecular Delivery and Metabolic Function in the Brain Endothelial Cells

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the coronavirus disease (COVID-19), is currently infecting millions of people worldwide and is causing drastic changes in people’s lives. Recent studies have shown that neurological symptoms are a major issue for people infected with SARS-CoV-2. However, the mechanism through which the pathological effects emerge is still unclear. Brain endothelial cells (ECs), one of the components of the blood–brain barrier, are a major hurdle for the entry of pathogenic or infectious agents into the brain. They strongly express angiotensin converting enzyme 2 (ACE2) for its normal physiological function, which is also well-known to be an opportunistic receptor for SARS-CoV-2 spike protein, facilitating their entry into host cells. First, we identified rapid internalization of the receptor-binding domain (RBD) S1 domain (S1) and active trimer (Trimer) of SARS-CoV-2 spike protein through ACE2 in brain ECs. Moreover, internalized S1 increased Rab5, an early endosomal marker while Trimer decreased Rab5 in the brain ECs. Similarly, the permeability of transferrin and dextran was increased in S1 treatment but decreased in Trimer, respectively. Furthermore, S1 and Trimer both induced mitochondrial damage including functional deficits in mitochondrial respiration. Overall, this study shows that SARS-CoV-2 itself has toxic effects on the brain ECs including defective molecular delivery and metabolic function, suggesting a potential pathological mechanism to induce neurological signs in the brain.

Plant-like hooked miniature machines for on-leaf sensing and delivery

New sustainable strategies for preserving plants are crucial for tackling environmental challenges. Bioinspired soft and miniature machines have the potential to operate in forests and agricultural fields by adapting their morphology to plant organs like leaves. However, applications on leaf surfaces are limited due to the fragility and heterogeneity of leaves, and harsh outdoor conditions. Here, we exploit the strong shear-dependent leaf-attachment of the hook-climber Galium aparine to create miniature systems that enable precision anchoring to leaf tissues via multifunctional microhooks. We first study the anchoring forces of the microhooks and then fabricate a soft wireless multiparameter sensor to monitor the leaf proximity and degradable hooks for in-plant molecular delivery to the vascular tissues of the leaves. In addition, we use a soft robotic proof-of-concept demonstrator to highlight how our hooks enable ratchet-like motion on leaves. This research showcases opportunities for specifically designing multifunctional machines for targeted applications in plant ecosystems.

Cu (II)-triggered release system by L- cysteine functionalized gold nanoparticles for “on-demand” molecular delivery and bioimaging in cells

Functionalized gold nanoparticles (GNP) has been extensively studied for cargo delivery and imaging towards biomedical applications. However, their are limited studies showcasing the above two in sync using GNP. In...

Foreign body responses in mouse central nervous system mimic natural wound responses and alter biomaterial functions

Biomaterials hold promise for therapeutic applications in the central nervous system (CNS). Little is known about molecular factors that determine CNS foreign body responses (FBRs) in vivo, or about how such responses influence biomaterial function. Here, we probed these factors in mice using a platform of injectable hydrogels readily modified to present interfaces with different physiochemical properties to host cells. We found that biomaterial FBRs mimic specialized multicellular CNS wound responses not present in peripheral tissues, which serve to isolate damaged neural tissue and restore barrier functions. We show that the nature and intensity of CNS FBRs are determined by definable properties that significantly influence hydrogel functions, including resorption and molecular delivery when injected into healthy brain or stroke injuries. Cationic interfaces elicit stromal cell infiltration, peripherally derived inflammation, neural damage and amyloid production. Nonionic and anionic formulations show minimal levels of these responses, which contributes to superior bioactive molecular delivery. Our results identify specific molecular mechanisms that drive FBRs in the CNS and have important implications for developing effective biomaterials for CNS applications.