scholarly journals Poroelastic Attributes: A Real-time Determinant Membrane Nanorheology for Receptor Dependent Endocytosis of Targeted Gold Nanoparticles

2021 ◽  
Author(s):  
Tanmay Abhay Kulkarni ◽  
Debabrata Mukhopadhyay ◽  
Santanu Bhattacharya
Keyword(s):  
Drug Delivery ◽  
Gold Nanoparticles ◽  
Shear Stress ◽  
Diffusion Coefficient ◽  
Cell Membrane ◽  
Pore Size ◽  
Surface Engineering ◽  
Diffusion Constant ◽  
Uptake Mechanism ◽  
Receptor Mediated Endocytosis

Abstract BackgroundEfficacy of targeted drug delivery using nanoparticles relies on several factors including the uptake mechanisms such as phagocytosis, macropinocytosis, micropinocytosis and receptor mediated endocytosis. These mechanisms have been studied with respect to the alteration in signaling mechanisms, cellular morphology, and linear nanomechanical properties (NMPs). Commonly employed classical contact mechanics models to address cellular NMPs fail to address mesh like structure consisting of bilayer lipids and proteins of cell membrane. To overcome this technical challenge, we employed poroelastic model which accounts for the biphasic nature of cells including their porous behavior exhibiting both solid like (fluid storage) and liquid like (fluid dissipate) behavior ResultsIn this study, we employed atomic force microscopy to monitor the influence of surface engineering of gold nanoparticles (GNPs) to the alteration of nonlinear NMPs such as drained Poisson’s ratio, effective shear stress, diffusion constant and pore dimensions of cell membranes during their uptake. Herein, we used pancreatic cancer (PDAC) cell lines including Panc1, AsPC-1 and endothelial cell HUVECs to understand the receptor-dependent and -independent endocytosis of two different GNPs derived using plectin-1 targeting peptide (PTP-GNP) and corresponding scrambled peptide (sPEP-GNP). Compared to untreated cells, in case of receptor dependent endocytosis of PTP-GNPs diffusion coefficient altered ~1264-fold and ~1530-fold and pore size altered ~320-fold and ~260-fold in Panc1 and AsPC-1 cells respectively. Whereas for receptor independent mechanisms, we observed modest alteration in diffusion coefficient and pore size, in these cells compared to untreated cells. Effective shear stress corresponding to 7.38±0.15 kPa and 20.49±0.39 kPa in PTP-GNP treatment in Panc1 and AsPC-1, respectively was significantly more than that for sPEP-GNP. These results demonstrate that with temporal recruitment of plectin-1 during receptor mediated endocytosis affects the poroelastic attributes of the membrane. ConclusionThis study confirms that nonlinear NMPs of cell membrane are directly associated with the uptake mechanism of nanoparticles and can provide promising insights of the nature of endocytosis mechanism involved for organ specific drug delivery using nanoparticles. Hence, nanomechanical analysis of cell membrane es using this noninvasive, label-free and live-cell analytical tool can therefore be instrumental to evaluate therapeutic benefit of nanoformulations.

scholarly journals Investigation of an Optical Imaging Platform Integrated with an Ultrasound Application System for In Vitro Verification of Ultrasound-Mediated Drug Delivery

2021 ◽  
Vol 11 (6) ◽  
pp. 2846
Author(s):  
Jong-ryul Choi ◽  
Juyoung Park
Keyword(s):  
Drug Delivery ◽  
Cervical Cancer ◽  
Cell Membrane ◽  
Optical Imaging ◽  
Cancer Cell ◽  
Fluorescent Imaging ◽  
Calcium Flux ◽  
Cervical Cancer Cell ◽  
Application System ◽  
Ultrasound Application

Techniques that increase the permeability of the cell membrane and transfer drugs or genes to cells have been actively developed as effective therapeutic modalities. Also, in line with the development of these drug delivery techniques, the establishment of tools to verify the techniques at the cellular level is strongly required. In this study, we demonstrated an optical imaging platform integrated with an ultrasound application system to verify the feasibility of safe and efficient drug delivery through the cell membrane using ultrasound-microbubble cavitation. To examine the potential of the platform, fluorescence images of both Fura-2 AM and propidium iodide (PI) to measure calcium flux changes and intracellular PI delivery, respectively, during and after the ultrasound-microbubble cavitation in the cervical cancer cell were acquired. Using the optical imaging platform, we determined that calcium flux increased immediately after the ultrasound-microbubble cavitation and were restored to normal levels, and fluorescence signals from intracellular PI increased gradually after the cavitation. The results acquired by the platform indicated that ultrasound-microbubble cavitation can deliver PI into the cervical cancer cell without irreversible damage of the cell membrane. The application of an additional fluorescent imaging module and high-speed imaging modalities can provide further improvement of the performance of this platform. Also, as additional studies in ultrasound instrumentations to measure real-time cavitation signals progress, we believe that the ultrasound-microbubble cavitation-based sonoporation can be employed for safe and efficient drug and gene delivery to various cancer cells.

scholarly journals Anomalous Diffusion with an Apparently Negative Diffusion Coefficient in a One-Dimensional Quantum Molecular Chain Model

Symmetry ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 506
Author(s):  
Sho Nakade ◽  
Kazuki Kanki ◽  
Satoshi Tanaka ◽  
Tomio Petrosky
Keyword(s):  
Diffusion Coefficient ◽  
Diffusion Constant ◽  
Mean Square Displacement ◽  
Second Law Of Thermodynamics ◽  
Molecular Chain ◽  
Chain Model ◽  
Phase Mixing ◽  
One Dimensional ◽  
The One ◽  
Negative Diffusion

An interesting anomaly in the diffusion process with an apparently negative diffusion coefficient defined through the mean-square displacement in a one-dimensional quantum molecular chain model is shown. Nevertheless, the system satisfies the H-theorem so that the second law of thermodynamics is satisfied. The reason why the “diffusion constant” becomes negative is due to the effect of the phase mixing process, which is a characteristic result of the one-dimensionality of the system. We illustrate the situation where this negative “diffusion constant” appears.

Diffusion of Heavy Oil in SiO2 Model Catalyst and FCC Catalyst

2012 ◽  
Vol 550-553 ◽  
pp. 158-163 ◽  
Author(s):  
Zi Yuan Liu ◽  
Sheng Li Chen ◽  
Peng Dong ◽  
Xiu Jun Ge
Keyword(s):  
Diffusion Coefficient ◽  
Pore Size ◽  
Effective Diffusion Coefficient ◽  
Pore Diameter ◽  
Effective Diffusion ◽  
Model Catalyst ◽  
Average Pore ◽  
Diffusion Factor ◽  
Fcc Catalyst ◽  
Fcc Catalysts

Through the measured effective diffusion coefficients of Dagang vacuum residue supercritical fluid extraction and fractionation (SFEF) fractions in FCC catalysts and SiO2model catalysts, the relation between pore size of catalyst and effective diffusion coefficient was researched and the restricted diffusion factor was calculated. The restricted diffusion factor in FCC catalysts is less than 1 and it is 1~2 times larger in catalyst with polystyrene (PS) template than in conventional FCC catalyst without template, indicating that the diffusion of SFEF fractions in the two FCC catalysts is restricted by the pore. When the average molecular diameter is less than 1.8 nm, the diffusion of SFEF fractions in SiO2model catalyst which average pore diameter larger than 5.6 nm is unrestricted. The diffusion is restricted in the catalyst pores of less than 8 nm for SFEF fractions which diameter more than 1.8 nm. The tortuosity factor of SiO2model catalyst is obtained to be 2.87, within the range of empirical value. The effective diffusion coefficient of the SFEF fractions in SiO2model catalyst is two orders of magnitude larger than that in FCC catalyst with the same average pore diameter. This indicate that besides the ratio of molecular diameter to the pore diameter λ, the effective diffusion coefficient is also closely related to the pore structure of catalyst. Because SiO2model catalyst has uniform pore size, the diffusion coefficient can be precisely correlated with pore size of catalyst, so it is a good model material for catalyst internal diffusion investigation.

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