Materials patterned with high-aspect-ratio nanostructures have features on similar length scales to cellular components. These surfaces are an extreme topography on the cellular level and have become useful tools for perturbing and sensing the cellular environment. Motivation comes from the ability of high-aspect-ratio nanostructures to deliver cargoes into cells and tissues, access the intracellular environment, and control cell behavior. These structures directly perturb cells' ability to sense and respond to external forces, influencing cell fate, and enabling new mechanistic studies. Through careful design of their nanoscale structure, these systems act as biological metamaterials, eliciting unusual biological responses. While predominantly used to interface eukaryotic cells, there is growing interest in nonanimal and prokaryotic cell interfacing. Both experimental and theoretical studies have attempted to develop a mechanistic understanding for the observed behaviors, predominantly focusing on the cell-nanostructure interface. This review considers how high-aspect-ratio nanostructured surfaces are used to both stimulate and sense biological systems.

/pdf/high-aspect-ratio-nanostructured-surfaces-as-biological-4lbi856znm.pdf

High-Aspect-Ratio Nanostructured Surfaces as Biological Metamaterials

GaN microneedle crystals are grown via GaAs substrates decomposition, using ultrahigh‐pure anhydrous ammonia as nitrogen precursor at 900 °C for 4 min. The X‐ray diffraction pattern shows the possible cubic and hexagonal coexistence of phases for the GaN highest intensity peak. Scanning electron microscopy presents a seaflower‐type growth for GaN microneedles, which can be related to factors such as lattice mismatch and substrate roughness due to the cleaning process. On the other hand, energy‐dispersive spectroscopy and X‐ray photoelectron spectroscopy characterizations demonstrate the elemental contributions of gallium and nitrogen for the GaN microneedle. Transmission electron microscopy shows uniform growth with an interplanar spacing of 2.76 Å. In addition, a possible growth model by hexagonal crystals stacking is proposed for obtaining GaN microneedles using the mechanism of Volmer–Weber growth. Photoluminescence spectrum presents an energy emission peak in the ultraviolet band with a value of 3.40 eV (364 nm), which is related to the band‐to‐band transition, and Raman scattering shows stress in the GaN microneedles due to the presence of different vibration modes for hexagonal GaN, indicating that several microneedles break.

Optical and Structural Analysis of GaN Microneedle Crystals Obtained via GaAs Substrates Decomposition and their Possible Growth Model Using the Volmer–Weber Mechanism

Intracellular delivery strategies are critical to the application of gene delivery, cell therapy, induced pluripotent stem cells, etc. Traditional methods such as viruses, liposomes, and electroporation always lead to high toxicity and cell damage, therefore, their applications can be limited. The mechanical method based on biological probes is less harmful to cells and keep the cell activities. Molecules can be delivered into the living cell quite accurately as well. So, the mechanical method is getting more and more attention. Biological probes methods include microinjection, nanotips and nanoneedle array, the following overview introduces the characteristics and applications of these three methods. In the end, we compared the advantages and disadvantages of these three methods and we make the prospects for subsequent development. 

Overview of Living Cell Delivery Method Based on Biological Probe

Simulation and experimental study on the influence of lamina on nanoneedle penetration into the cell nucleus

HLA antigen presentation and T-cell mediated immunity are critical to control acute viral infection such as COVID-19 caused by SARS-CoV-2. Recent data suggest that both the depth of peptide presentation and the breadth of the T-cell repertoire are associated with disease outcome. It has also been shown that unexposed subjects can develop strong T-cell responses against SARS-CoV-2 due to heterologous immunity. In this study, we explored the anti-SARS-CoV-2 T-cell repertoire by analyzing previously published T-cell receptor (TCR) CDR3β immunosequencing data in a cohort of 116 healthy donors and in the context of immune reconstitution after allogeneic hematopoietic stem cell transplantation in 116 recipients collected during the pre-COVID-19 era. For this, 143,310 publicly available SARS-CoV-2 specific T-cell sequences were investigated among the 3.5 million clonotypes in the cohort. We also performed HLA class I peptide binding predictions using the reference proteome of the virus and high resolution genotyping data in these patients. We could demonstrate that individuals are fully equipped at the genetic level to recognize SARS-CoV-2. This is evidenced by the 5% median cumulative frequency of clonotypes having their sequence matched to a SARS-CoV-2 specific T-cell. In addition, any combination of HLA class I variants in this cohort is associated with a broad capacity of presenting hundreds of SARS-CoV-2 derived peptides. These results could be explained by heterologous immunity and random somatic TCR recombination. We speculate that these observations could explain the efficacy of the specific immune response against SARS-CoV-2 in individuals without risk factors of immunodeficiency and infected prior to vaccination. 

<scp>HLA</scp> variants and <scp>TCR</scp> diversity against <scp>SARS‐CoV</scp>‐2 in the <scp>pre‐COVID</scp>‐19 era

Functionalized inclined-GaN based nanoneedles

The COVID-19 pandemic has caused a health crisis worldwide; therefore, it is necessary to understand the factors related to its prognosis. In this study, we hypothesized that SARS-CoV-2-derived antigens presented by MHC class I may correlate with mortality in COVID-19 because they induce adaptive immune responses. Antigen coverage at the national level was inferred using country-specific HLA allele frequencies and relative predictions of binding antigens. We performed regression analysis between antigen coverage and the death rate due to COVID-19 across countries and found a negative correlation, although it was statistically significant only in HLA-B. This negative correlation was corroborated in multiple regression analysis with known risk factors, such as the prevalence of underlying disease. Furthermore, we analyzed antigen coverage in accordance with SARS-CoV-2 domains and identified a significant negative correlation when it was derived from the spike domain, which is reported to be favorable for COVID-19 prognosis. Taken together, the results indicate that the antigen coverage of SARS-CoV-2 specifically presented by HLA-B may act as a favorable factor when explaining COVID-19-induced mortality

/pdf/antigen-coverage-presented-by-mhc-class-i-has-a-negative-3rrhxfsy.pdf

Antigen Coverage Presented by MHC Class I Has a Negative Correlation with SARS-CoV-2-Induced Mortality

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/ctm2.714

Gene essentiality for tumour growth influences neoantigen‐directed immunoediting

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Functionalized inclined-GaN based nanoneedles

Antigen Coverage Presented by MHC Class I Has a Negative Correlation with SARS-CoV-2-Induced Mortality

Gene essentiality for tumour growth influences neoantigen‐directed immunoediting