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

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

The probability of the formation of specific bonds increases in the presence of free proteins in the medium.This is shown by the frequency of the appearance of multi jump-out peaks pattern describing specific rupture and unfolding events during the retraction curves in Group I measured in M (grey) and Group II measured in ComM (black).
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f8: The probability of the formation of specific bonds increases in the presence of free proteins in the medium.This is shown by the frequency of the appearance of multi jump-out peaks pattern describing specific rupture and unfolding events during the retraction curves in Group I measured in M (grey) and Group II measured in ComM (black).

Mentions: The above observations obtained from the load curves that show a striking difference in the tip-cell interactions between the two groups are in line with the results of the work of adhesion derived from the unloading curves, as summarized in Fig. 6c. Long-ranged pull-off forces resulting in a large work of adhesion as demonstrated in Fig. 4 (pink curve) are related to bonding events such as tethering of receptors to ligands, and clamping of a trans-membranal protein or any other biomacromolecule by the tip5354. In addition, simple nonspecific adhesion arising from van der Waals interaction may be playing a minor role. Multi jump-out peaks in a “sawtooth” pattern observed in the unload curves indicate serial rupture of specific bonds or unfolding of macromolecules before full separation between the tip and the cell is retrieved. The rupture force, as observed in the unloading curves, is several tens of pN which is in agreement with specific ligand-receptor data given in the literature5556. The probability of these processes increases dramatically in a ComM environment (Group II) due to the presence of many proteins which may bridge the tip to the cell surface. Based on the above, the frequency of the appearance of multi-peaks pattern during the retraction of the tip is expected to be much higher in Group II. This is indeed the case as explicitly shown in Fig. 8. Additionally, the large adhesion shown in Group II is consistent with the large indentation since, on geometrical grounds, the contact area of the tip with the cell surface varies as the square of the indentation enabling the formation of additional specific bonds. Moreover, due to the large indentation the tip spends a longer time in contact with the cell, which allows the formation of these specific bonds contributing to the increase in work of adhesion. We note that the only other AFM study we know of that compared surface-cell interactions in serum containing and serum free media utilized much larger, colloidal probes, of 8–10 μm diameter and demonstrated a twofold increase in the adhesion force between microspheres and cells in the presence of serum57.


The effect of the serum corona on interactions between a single nano-object and a living cell
The probability of the formation of specific bonds increases in the presence of free proteins in the medium.This is shown by the frequency of the appearance of multi jump-out peaks pattern describing specific rupture and unfolding events during the retraction curves in Group I measured in M (grey) and Group II measured in ComM (black).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5382918&req=5

f8: The probability of the formation of specific bonds increases in the presence of free proteins in the medium.This is shown by the frequency of the appearance of multi jump-out peaks pattern describing specific rupture and unfolding events during the retraction curves in Group I measured in M (grey) and Group II measured in ComM (black).
Mentions: The above observations obtained from the load curves that show a striking difference in the tip-cell interactions between the two groups are in line with the results of the work of adhesion derived from the unloading curves, as summarized in Fig. 6c. Long-ranged pull-off forces resulting in a large work of adhesion as demonstrated in Fig. 4 (pink curve) are related to bonding events such as tethering of receptors to ligands, and clamping of a trans-membranal protein or any other biomacromolecule by the tip5354. In addition, simple nonspecific adhesion arising from van der Waals interaction may be playing a minor role. Multi jump-out peaks in a “sawtooth” pattern observed in the unload curves indicate serial rupture of specific bonds or unfolding of macromolecules before full separation between the tip and the cell is retrieved. The rupture force, as observed in the unloading curves, is several tens of pN which is in agreement with specific ligand-receptor data given in the literature5556. The probability of these processes increases dramatically in a ComM environment (Group II) due to the presence of many proteins which may bridge the tip to the cell surface. Based on the above, the frequency of the appearance of multi-peaks pattern during the retraction of the tip is expected to be much higher in Group II. This is indeed the case as explicitly shown in Fig. 8. Additionally, the large adhesion shown in Group II is consistent with the large indentation since, on geometrical grounds, the contact area of the tip with the cell surface varies as the square of the indentation enabling the formation of additional specific bonds. Moreover, due to the large indentation the tip spends a longer time in contact with the cell, which allows the formation of these specific bonds contributing to the increase in work of adhesion. We note that the only other AFM study we know of that compared surface-cell interactions in serum containing and serum free media utilized much larger, colloidal probes, of 8–10 μm diameter and demonstrated a twofold increase in the adhesion force between microspheres and cells in the presence of serum57.

View Article: PubMed Central - PubMed

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus