scholarly journals Designed and biologically active protein lattices

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shih-Ting Wang ◽  
Brian Minevich ◽  
Jianfang Liu ◽  
Honghu Zhang ◽  
Dmytro Nykypanchuk ◽  
...  

AbstractVersatile methods to organize proteins in space are required to enable complex biomaterials, engineered biomolecular scaffolds, cell-free biology, and hybrid nanoscale systems. Here, we demonstrate how the tailored encapsulation of proteins in DNA-based voxels can be combined with programmable assembly that directs these voxels into biologically functional protein arrays with prescribed and ordered two-dimensional (2D) and three-dimensional (3D) organizations. We apply the presented concept to ferritin, an iron storage protein, and its iron-free analog, apoferritin, in order to form single-layers, double-layers, as well as several types of 3D protein lattices. Our study demonstrates that internal voxel design and inter-voxel encoding can be effectively employed to create protein lattices with designed organization, as confirmed by in situ X-ray scattering and cryo-electron microscopy 3D imaging. The assembled protein arrays maintain structural stability and biological activity in environments relevant for protein functionality. The framework design of the arrays then allows small molecules to access the ferritins and their iron cores and convert them into apoferritin arrays through the release of iron ions. The presented study introduces a platform approach for creating bio-active protein-containing ordered nanomaterials with desired 2D and 3D organizations.

Author(s):  
Kathleen M. Marr ◽  
Mary K. Lyon

Photosystem II (PSII) is different from all other reaction centers in that it splits water to evolve oxygen and hydrogen ions. This unique ability to evolve oxygen is partly due to three oxygen evolving polypeptides (OEPs) associated with the PSII complex. Freeze etching on grana derived insideout membranes revealed that the OEPs contribute to the observed tetrameric nature of the PSIl particle; when the OEPs are removed, a distinct dimer emerges. Thus, the surface of the PSII complex changes dramatically upon removal of these polypeptides. The atomic force microscope (AFM) is ideal for examining surface topography. The instrument provides a topographical view of individual PSII complexes, giving relatively high resolution three-dimensional information without image averaging techniques. In addition, the use of a fluid cell allows a biologically active sample to be maintained under fully hydrated and physiologically buffered conditions. The OEPs associated with PSII may be sequentially removed, thereby changing the surface of the complex by one polypeptide at a time.


2021 ◽  
Vol 21 ◽  
Author(s):  
Madhukar Garg ◽  
Anju Goyal ◽  
Sapna Kumari

: Cubosomes are highly stable nanostructured liquid crystalline dosage delivery form derived from amphiphilic lipids and polymer-based stabilizers converting it in a form of effective biocompatible carrier for the drug delivery. The delivery form comprised of bicontinuous lipid bilayers arranged in three dimensional honeycombs like structure provided with two internal aqueous channels for incorporation of number of biologically active ingredients. In contrast liposomes they provide large surface area for incorporation of different types of ingredients. Due to the distinct advantages of biocompatibility and thermodynamic stability, cubosomes have remained the first preference as method of choice in the sustained release, controlled release and targeted release dosage forms as new drug delivery system for the better release of the drugs. As lot of advancement in the new form of dosage form has bring the novel avenues in drug delivery mechanisms so it was matter of worth to compile the latest updates on the various aspects of mentioned therapeutic delivery system including its structure, routes of applications along with the potential applications to encapsulate variety drugs to serve health related benefits.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kiyoshi Masuyama ◽  
Tomoaki Higo ◽  
Jong-Kook Lee ◽  
Ryohei Matsuura ◽  
Ian Jones ◽  
...  

AbstractIn contrast to hypertrophic cardiomyopathy, there has been reported no specific pattern of cardiomyocyte array in dilated cardiomyopathy (DCM), partially because lack of alignment assessment in a three-dimensional (3D) manner. Here we have established a novel method to evaluate cardiomyocyte alignment in 3D using intravital heart imaging and demonstrated homogeneous alignment in DCM mice. Whilst cardiomyocytes of control mice changed their alignment by every layer in 3D and position twistedly even in a single layer, termed myocyte twist, cardiomyocytes of DCM mice aligned homogeneously both in two-dimensional (2D) and in 3D and lost myocyte twist. Manipulation of cultured cardiomyocyte toward homogeneously aligned increased their contractility, suggesting that homogeneous alignment in DCM mice is due to a sort of alignment remodelling as a way to compensate cardiac dysfunction. Our findings provide the first intravital evidence of cardiomyocyte alignment and will bring new insights into understanding the mechanism of heart failure.


2021 ◽  
Vol 7 (3) ◽  
pp. 209-219
Author(s):  
Iris J Holzleitner ◽  
Alex L Jones ◽  
Kieran J O’Shea ◽  
Rachel Cassar ◽  
Vanessa Fasolt ◽  
...  

Abstract Objectives A large literature exists investigating the extent to which physical characteristics (e.g., strength, weight, and height) can be accurately assessed from face images. While most of these studies have employed two-dimensional (2D) face images as stimuli, some recent studies have used three-dimensional (3D) face images because they may contain cues not visible in 2D face images. As equipment required for 3D face images is considerably more expensive than that required for 2D face images, we here investigated how perceptual ratings of physical characteristics from 2D and 3D face images compare. Methods We tested whether 3D face images capture cues of strength, weight, and height better than 2D face images do by directly comparing the accuracy of strength, weight, and height ratings of 182 2D and 3D face images taken simultaneously. Strength, height and weight were rated by 66, 59 and 52 raters respectively, who viewed both 2D and 3D images. Results In line with previous studies, we found that weight and height can be judged somewhat accurately from faces; contrary to previous research, we found that people were relatively inaccurate at assessing strength. We found no evidence that physical characteristics could be judged more accurately from 3D than 2D images. Conclusion Our results suggest physical characteristics are perceived with similar accuracy from 2D and 3D face images. They also suggest that the substantial costs associated with collecting 3D face scans may not be justified for research on the accuracy of facial judgments of physical characteristics.


2021 ◽  
pp. 039139882098680
Author(s):  
Xuefeng Zhang ◽  
Nan Wang ◽  
Yuhua Huang ◽  
Yan Li ◽  
Gang Li ◽  
...  

Background: Three-dimensional (3D) culture has been reported to increase the therapeutic potential of mesenchymal stem cells (MSCs). The present study assessed the therapeutic efficacy of extracellular vesicles (EVs) from 3D cultures of human placental MSCs (hPMSCs) for acute kidney injury (AKI). Methods: The supernatants from monolayer culture (2D) and 3D culture of hPMSCs were ultra-centrifuged for EVs isolation. C57BL/6 male mice were submitted to 45 min bilateral ischemia of kidney, followed by renal intra-capsular administration of EVs within a 72 h reperfusion period. Histological, immunohistochemical, and ELISA analyses of kidney samples were performed to evaluate cell death and inflammation. Kidney function was evaluated by measuring serum creatinine and urea nitrogen. The miRNA expression profiles of EVs from 2D and 3D culture of hPMSCs were evaluated using miRNA microarray analysis. Results: The 3D culture of hPMSCs formed spheroids with different diameters depending on the cell density seeded. The hPMSCs produced significantly more EVs in 3D culture than in 2D culture. More importantly, injection of EVs from 3D culture of hPMSCs into mouse kidney with ischemia-reperfusion (I/R)-AKI was more beneficial in protecting from progression of I/R than those from 2D culture. The EVs from 3D culture of hPMSCs were more efficient against apoptosis and inflammation than those from 2D culture, which resulted in a reduction in tissue damage and amelioration of renal function. MicroRNA profiling analysis revealed that a set of microRNAs were significantly changed in EVs from 3D culture of hPMSCs, especially miR-93-5p. Conclusion: The EVs from 3D culture of hPMSCs have therapeutic potential for I/R-AKI.


2021 ◽  
Author(s):  
Serge Marbacher ◽  
Matthias Halter ◽  
Deborah R Vogt ◽  
Jenny C Kienzler ◽  
Christian T J Magyar ◽  
...  

Abstract BACKGROUND The current gold standard for evaluation of the surgical result after intracranial aneurysm (IA) clipping is two-dimensional (2D) digital subtraction angiography (DSA). While there is growing evidence that postoperative 3D-DSA is superior to 2D-DSA, there is a lack of data on intraoperative comparison. OBJECTIVE To compare the diagnostic yield of detection of IA remnants in intra- and postoperative 3D-DSA, categorize the remnants based on 3D-DSA findings, and examine associations between missed 2D-DSA remnants and IA characteristics. METHODS We evaluated 232 clipped IAs that were examined with intraoperative or postoperative 3D-DSA. Variables analyzed included patient demographics, IA and remnant distinguishing characteristics, and 2D- and 3D-DSA findings. Maximal IA remnant size detected by 3D-DSA was measured using a 3-point scale of 2-mm increments. RESULTS Although 3D-DSA detected all clipped IA remnants, 2D-DSA missed 30.4% (7 of 23) and 38.9% (14 of 36) clipped IA remnants in intraoperative and postoperative imaging, respectively (95% CI: 30 [ 12, 49] %; P-value .023 and 39 [23, 55] %; P-value = <.001), and more often missed grade 1 (< 2 mm) clipped remnants (odds ratio [95% CI]: 4.3 [1.6, 12.7], P-value .005). CONCLUSION Compared with 2D-DSA, 3D-DSA achieves a better diagnostic yield in the evaluation of clipped IA. Our proposed method to grade 3D-DSA remnants proved to be simple and practical. Especially small IA remnants have a high risk to be missed in 2D-DSA. We advocate routine use of either intraoperative or postoperative 3D-DSA as a baseline for lifelong follow-up of clipped IA.


2021 ◽  
pp. 021849232110304
Author(s):  
Mehrnoush Toufan ◽  
Zahra Jabbary ◽  
Naser Khezerlou aghdam

Background To quantify valvular morphological assessment, some two-dimensional (2D) and three-dimensional (3D) scoring systems have been developed to target the patients for balloon mitral valvuloplasty; however, each scoring system has some potential limitations. To achieve the best scoring system with the most features and the least restrictions, it is necessary to check the degree of overlap of these systems. Also the factors related to the accuracy of these systems should be studied. We aimed to determine the correlation between the 2D Wilkins and real-time transesophageal three-dimensional (RT3D-TEE) scoring systems. Methods This cross-sectional study was performed on 156 patients with moderate to severe mitral stenosis who were candidates for percutaneous balloon valvuloplasty. To morphologic assessment of mitral valve, patients were examined by 2D-transthoracic echocardiography and RT3D-TEE techniques on the same day. Results A strong association was found between total Wilkins and total RT3D-TEE scores (r = 0.809, p < 0.001). The mean mitral valve area assessed by the 2D and 3D was 1.07 ± 0.25 and 1.03 ± 0.26, respectively, indicating a mean difference of 0.037 cm2 (p = 0.001). We found a strong correlation between the values of mitral valve area assessed by 2D and 3D techniques (r = 0.846, p < 0.001). Conclusion There is a high correlation between the two scoring systems in terms of evaluating dominant morphological features. Partially, mitral valve area overestimation in the 2D-transthoracic echocardiography and its inability to assess commissural involvement as well as its dependence on patient age were exceptions in this study.


2021 ◽  
Vol 8 (1) ◽  
pp. 11
Author(s):  
Sorel E. De Leon ◽  
Lana Cleuren ◽  
Zay Yar Oo ◽  
Paul R. Stoddart ◽  
Sally L. McArthur

Three-dimensional (3D) cell cultures have recently emerged as tools for biologically modelling the human body. As 3D models make their way into laboratories there is a need to develop characterisation techniques that are sensitive enough to monitor the cells in real time and without the need for chemical labels. Impedance spectroscopy has been shown to address both of these challenges, but there has been little research into the full impedance spectrum and how the different components of the system affect the impedance signal. Here we investigate the impedance of human fibroblast cells in 2D and 3D collagen gel cultures across a broad range of frequencies (10 Hz to 5 MHz) using a commercial well with in-plane electrodes. At low frequencies in both 2D and 3D models it was observed that protein adsorption influences the magnitude of the impedance for the cell-free samples. This effect was eliminated once cells were introduced to the systems. Cell proliferation could be monitored in 2D at intermediate frequencies (30 kHz). However, the in-plane electrodes were unable to detect any changes in the impedance at any frequency when the cells were cultured in the 3D collagen gel. The results suggest that in designing impedance measurement devices, both the nature and distribution of the cells within the 3D culture as well as the architecture of the electrodes are key variables.


2021 ◽  
Vol 379 (5) ◽  
Author(s):  
Giovanna Li Petri ◽  
Maria Valeria Raimondi ◽  
Virginia Spanò ◽  
Ralph Holl ◽  
Paola Barraja ◽  
...  

AbstractThe five-membered pyrrolidine ring is one of the nitrogen heterocycles used widely by medicinal chemists to obtain compounds for the treatment of human diseases. The great interest in this saturated scaffold is enhanced by (1) the possibility to efficiently explore the pharmacophore space due to sp3-hybridization, (2) the contribution to the stereochemistry of the molecule, (3) and the increased three-dimensional (3D) coverage due to the non-planarity of the ring—a phenomenon called “pseudorotation”. In this review, we report bioactive molecules with target selectivity characterized by the pyrrolidine ring and its derivatives, including pyrrolizines, pyrrolidine-2-one, pyrrolidine-2,5-diones and prolinol described in the literature from 2015 to date. After a comparison of the physicochemical parameters of pyrrolidine with the parent aromatic pyrrole and cyclopentane, we investigate the influence of steric factors on biological activity, also describing the structure–activity relationship (SAR) of the studied compounds. To aid the reader’s approach to reading the manuscript, we have planned the review on the basis of the synthetic strategies used: (1) ring construction from different cyclic or acyclic precursors, reporting the synthesis and the reaction conditions, or (2) functionalization of preformed pyrrolidine rings, e.g., proline derivatives. Since one of the most significant features of the pyrrolidine ring is the stereogenicity of carbons, we highlight how the different stereoisomers and the spatial orientation of substituents can lead to a different biological profile of drug candidates, due to the different binding mode to enantioselective proteins. We believe that this work can guide medicinal chemists to the best approach in the design of new pyrrolidine compounds with different biological profiles.


Sign in / Sign up

Export Citation Format

Share Document