High-resolution microrheology in the pericellular matrix of prostate cancer cells

Nijenhuis, Nadja; Mizuno, Daisuke; Spaan, Jos A. E.; Schmidt, Christoph F.

doi:10.1098/rsif.2011.0825

Cited by 25 publications

(31 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…19 It has been reported that the PCM can reduce the ability of small molecules such as DNA 18,26 and sodium ions 27 to penetrate into cells. Thus, it is surprising that the PCM can recruit AuNPs and assist their cellular internalization.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Pericellular Matrix Enhances Retention and Cellular Uptake of Nanoparticles

Zhou

Xiong

et al. 2012

J. Am. Chem. Soc.

View full text Add to dashboard Cite

A hydrated gel-like pericellular matrix (PCM) covers the surface of all eukaryotic cells and plays a key role in many cellular events, but its effect on nanoparticle internalization has not been studied. Here, using cells with various PCM thicknesses and gold nanoparticles as probes, we demonstrate that, rather than being a barrier to all foreign objects, the PCM can entrap and accumulate NPs, restrict and slow down their diffusion, and enhance their cellular uptake efficiency. Moreover, this newly discovered PCM function consumes energy and seems to be an integral part of the receptor-mediated endocytosis process. These findings are important in understanding the delivery mechanisms of nanocarriers for biomedical applications.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Pericellular Matrix Enhances Retention and Cellular Uptake of Nanoparticles

Zhou

Xiong

et al. 2012

J. Am. Chem. Soc.

View full text Add to dashboard Cite

show abstract

“…In some cases this failure is dramatic[35]. Therefore, passive microrheology for characterizing the pericellular space has been limited to either detection of the formation of a hydrogel, dissolution of a hydrogel[36], or ECMs that are orders of magnitude softer than in vivo ECMs[37,38]. …”

Section: Resultsmentioning

confidence: 99%

Spatial distributions of pericellular stiffness in natural extracellular matrices are dependent on cell-mediated proteolysis and contractility

et al. 2017

View full text Add to dashboard Cite

Bulk tissue stiffness has been correlated with regulation of cellular processes and conversely cells have been shown to remodel their pericellular tissue according to a complex feedback mechanism critical to development, homeostasis, and disease. However, bulk rheological methods mask the dynamics within a heterogeneous fibrous extracellular matrix (ECM) in the region proximal to a cell (pericellular region). Here, we use optical tweezers active microrheology (AMR) to probe the distribution of the complex material response function (α = α′ + α″, in units of μm/nN) within a type I collagen ECM, a biomaterial commonly used in tissue engineering. We discovered cells both elastically and plastically deformed the pericellular material. α′ is wildly heterogeneous, with 1/α′ values spanning three orders of magnitude around a single cell. This was observed in gels having a cell-free 1/α′ of approximately 0.5 nN/μm. We also found that inhibition of cell contractility instantaneously softens the pericellular space and reduces stiffness heterogeneity, suggesting the system was strain hardened and not only plastically remodeled. The remaining regions of high stiffness strongly suggest cellular remodeling of their surrounding matrix. To test this hypothesis, cells were incubated within the type I collagen gel for 24 hours in a media containing a broad-spectrum matrix metalloproteinase (MMP) inhibitor. While the pericellular material maintained stiffness asymmetry, stiffness magnitudes were reduced. Dual inhibition demonstrates that the combination of MMP activity and contractility is necessary to establish the pericellular stiffness landscape. This heterogeneity in stiffness suggests the distribution of pericellular stiffness, and not bulk stiffness alone, must be considered in the study of cell-ECM interactions and design of complex biomaterial scaffolds.

show abstract

“…Visualization of the HA pericellular layer is less straightforward. There is a host of literature describing the use of fluorescent dyes to label the HA pericellular layer for endothelial cells (2,12,15,45), in which the HA layer has a rather well-defined boundary. Imaging of the HA layer on fibroblasts seems not to be as straightforward as on endothelial cells.…”

Section: Resultsmentioning

confidence: 99%

Pericellular Brush and Mechanics of Guinea Pig Fibroblast Cells Studied with AFM

Dokukin

Ablaeva

Kalaparthi

et al. 2016

Biophysical Journal

View full text Add to dashboard Cite

The atomic force microscopy (AFM) indentation method combined with the brush model can be used to separate the mechanical response of the cell body from deformation of the pericellular layer surrounding biological cells. Although self-consistency of the brush model to derive the elastic modulus of the cell body has been demonstrated, the model ability to characterize the pericellular layer has not been explicitly verified. Here we demonstrate it by using enzymatic removal of hyaluronic content of the pericellular brush for guinea pig fibroblast cells. The effect of this removal is clearly seen in the AFM force-separation curves associated with the pericellular brush layer. We further extend the brush model for brushes larger than the height of the AFM probe, which seems to be the case for fibroblast cells. In addition, we demonstrate that an extension of the brush model (i.e., double-brush model) is capable of detecting the hierarchical structure of the pericellular brush, which, for example, may consist of the pericellular coat and the membrane corrugation (microridges and microvilli). It allows us to quantitatively segregate the large soft polysaccharide pericellular coat from a relatively rigid and dense membrane corrugation layer. This was verified by comparison of the parameters of the membrane corrugation layer derived from the force curves collected on untreated cells (when this corrugation membrane part is hidden inside the pericellular brush layer) and on treated cells after the enzymatic removal of the pericellular coat part (when the corrugations are exposed to the AFM probe). We conclude that the brush model is capable of not only measuring the mechanics of the cell body but also the parameters of the pericellular brush layer, including quantitative characterization of the pericellular layer structure.

show abstract

High-resolution microrheology in the pericellular matrix of prostate cancer cells

Cited by 25 publications

References 48 publications

Pericellular Matrix Enhances Retention and Cellular Uptake of Nanoparticles

Pericellular Matrix Enhances Retention and Cellular Uptake of Nanoparticles

Spatial distributions of pericellular stiffness in natural extracellular matrices are dependent on cell-mediated proteolysis and contractility

Pericellular Brush and Mechanics of Guinea Pig Fibroblast Cells Studied with AFM

Contact Info

Product

Resources

About