Recording the dynamic endocytosis of single gold nanoparticles by AFM-based force tracing

Ding, Bohua; Tian, Ye; Pan, Yuqin; Shan, Yuping; Cai, Mingjun; Xu, Hao; Sun, Yingchun; Wang, Hongda

doi:10.1039/c5nr01020a

Cited by 25 publications

(23 citation statements)

References 29 publications

(26 reference statements)

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“…We used the “force tracing” technique based on AFM to follow the invagination of HEV7115 (setup is shown in Figure 1b). The AFM tip was engaged to the contact point between the AFM tip and cell surface (details are shown in Figure S3, Supporting Information).…”

Section: Resultsmentioning

confidence: 99%

The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations

Pan

Zhang

et al. 2017

Advanced Science

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Viral entry into the host cell is the first step of virus infection; however, its dynamic process via endocytosis remains largely elusive. Here, the force tracing technique and single particle simulation are combined to investigate the invagination of single human enterovirus 71 (HEV71, a positive single‐stranded RNA virus that is associated with hand, foot, and mouth disease) via cell membranes during its host cell entry. The experimental results reveal that the HEV71 invaginates in membrane vesicles at a force of 58 ± 16 pN, a duration time of 278 ± 68 ms. The simulation further shows that the virus can reach a partially wrapped state very fast, then the upper surface of the virus is covered by the membrane traveling over a long period of time. Combining the experiment with the simulation, the mechanism of membrane wrapping of virus is uncovered, which provides new insights into how the cell is operated to initiate the endocytosis of virus.

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Section: Resultsmentioning

confidence: 99%

The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations

Pan

Zhang

et al. 2017

Advanced Science

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“…7. Clearly complete endocytosis (as would be the case for a small NP31) cannot occur, since the AFM tip – whose footprint on the cell surface increases progressively as it indents the cell – cannot be ‘swallowed up’ by the cell.…”

Section: Resultsmentioning

confidence: 99%

“…We may then ask: why do we not observe any net attractive forces on approach , but only upon separation? A clue to this is provided by a recent study of endocytic forces on gold NPs31 Here the attractive endocytic forces on a 20 nm-diameter NP do not exceed ca.10 pN until the NP has been invaginated into the cell by about 10–15 nm. In the case of our 20 nm-diameter AFM tip, this would suggest that on initial contact and tip indentation of the cell surface by a comparable amount, the endocytic attraction on it would also be of that magnitude, ca.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, the question of cell-nanoparticle interaction has been addressed, so far, through investigation of the uptake process of specific particles4928. However, the direct measurement of the actual forces between a living cell and a nano-object has been much less addressed293031. The molecular force probe (MFP), a device based on an AFM platform but optimized to measure forces, provides the capability to directly examine the interaction between a nano-object and a single cell.…”

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confidence: 99%

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The effect of the serum corona on interactions between a single nano-object and a living cell

Dror

Sorkin

Brand

et al. 2017

Sci Rep

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Nanoparticles (NPs) which enter physiological fluids are rapidly coated by proteins, forming a so-called corona which may strongly modify their interaction with tissues and cells relative to the bare NPs. In this work the interactions between a living cell and a nano-object, and in particular the effect on this of the adsorption of serum proteins, are directly examined by measuring the forces arising as an Atomic Force Microscope tip (diameter 20 nm) - simulating a nano-object - approaches and contacts a cell. We find that the presence of a serum protein corona on the tip strongly modifies the interaction as indicated by pronounced increase in the indentation, hysteresis and work of adhesion compared to a bare tip. Classically one expects an AFM tip interacting with a cell surface to be repelled due to cell elastic distortion, offset by tip-cell adhesion, and indeed such a model fits the bare-tip/cell interaction, in agreement with earlier work. However, the force plots obtained with serum-modified tips are very different, indicating that the cell is much more compliant to the approaching tip. The insights obtained in this work may promote better design of NPs for drug delivery and other nano-medical applications.

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“…The method of linking a nano-drug to the AFM tip for single molecule "force tracing" tests has been proven effectively. 26,27 The main procedure of the "force tracing" based on AFM is shown in Fig. 2B; the deection of the AFM tip cantilever was indicated by a laser beam detected via a photodetector.…”

Section: -19mentioning

confidence: 99%

Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a “force tracing” technique

et al. 2018

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Considerable technological success has been achieved in the drug delivery of nano-drugs for chemotherapy, but the main obstacles in understanding the drug delivery dynamic mechanisms for nano-drug applications stem from technical limitations. In this paper, we explored the trans-membrane dynamic processes of polyamidoamine nano-drugs via a "force tracing" technique.Nanocarriers have been used as intelligent drug delivery systems (DDSs) to signicantly improve the bioavailability of poorly soluble drugs and the efficacy of drugs for clinical treatment.1-6 Among the many nanocarriers, polyamidoamine (PAMAM) dendrimers undoubtedly show a superior performance, attracting researchers' attention, 7 since they have the advantages of non-immunogenicity and a high transport efficiency for carrying bioactive agents.8 In addition, as PAMAM is sensitive to pH, the drug can be released from the interior of the macromolecule via diffusion, so as to achieve a sustained release and enhance the drug efficacy. In contrast to other nanocarriers, PAMAM dendrimers are highly branched synthetic macromolecules obtained via iterative stepwise reaction sequences, 9 and the highly branched structure ensures the facile modication of the dendrimer nanoparticle surface with different therapeutic drugs, diagnostic agents, and targeting ligands.10 The branched structure also makes it easy to conjugate with uorescein isothiocyanate for imaging live cells and tracking the drug carriers.11 The internal molecular cavity of PAMAM provides the ability to physically encase small molecule drugs through electrostatic interactions and/or hydrogen bonding interactions. 12Usually, covalent conjugation and encapsulation are the main methods for loading drugs on PAMAM. E. W. Meijer and coworkers reported that guest molecules were captured within the internal cavities of the dendritic nanoparticles, and that the diffusion of guest molecules out of the carriers into solution was slow because of the close packing of the shell.13 In order to understand the effect of drug loading on the structural properties of the dendrimer, V. Jain et al. used molecular dynamic (MD) simulations to characterize the molecular models of dendrimer-nateglinide encapsulation complexes, and the MD analysis revealed that both the pH value of the solution and the terminal groups of the dendrimer play a part in drug encapsulation efficiency.14 Another effective approach used in drug loading is the covalent conjugation of the drug to the terminal functional groups of the dendrimers.12 Y. Gao et al. successfully conjugated ursolic acid (UA) and folic acid (FA) to PAMAM, and a subsequent cellular uptake study indicated that the presence of FA enhanced the uptake of dendrimeric prodrugs by HeLa cells with over-expressed folate receptors (FRs). This effect could be attributed to FR-mediated endocytosis.15 R. Mohammad et al. developed PAMAM-pullulan conjugates and investigated their targeting activity in delivering genes into liver cells. Furthermore, they assessed the cytotoxicity and tra...

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Recording the dynamic endocytosis of single gold nanoparticles by AFM-based force tracing

Cited by 25 publications

References 29 publications

The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations

The Process of Wrapping Virus Revealed by a Force Tracing Technique and Simulations

The effect of the serum corona on interactions between a single nano-object and a living cell

Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a “force tracing” technique

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