Elucidating the role of matrix stiffness

Posted by / 17-Aug-2017 11:40

Tumor invasion and metastasis are strongly regulated by biophysical interactions between tumor cells and the extracellular matrix (ECM).

While the influence of ECM stiffness on cell migration, adhesion, and contractility has been extensively studied in 2D culture, extension of this concept to 3D cultures that more closely resemble tissue has proven challenging, because perturbations that change matrix stiffness often concurrently change cellular confinement.

Our combined results demonstrate that peptide-functionalized PEG hydrogels provide a useful platform for investigating aspects of tumor progression in 2D and 3D microenvironments, including single cell migration, cluster growth and invasion.

Tumor progression and metastasis are dependent on reciprocal changes between tumor cells and the local microenvironment, which includes genetic changes, cell-cell interactions, soluble signaling, and biochemical and biophysical extracellular matrix (ECM) properties.

We test these hypotheses in silico by devising a multiscale mathematical model that relates cellular force generation to ECM stiffness and geometry, which we show is capable of recapitulating key experimental trends.Over time, I’ll share it here and there, but what I eat is not at all the focus of this blog.I ask that you refrains for pursuing questions about what I eat in the comment section. For many people it’s so overwhelming to contrast what they currently eat – probably a typical American diet of 500-600 daily grams of carbohydrates (200 grams of which are sugar) – with a diet of less than 50 daily grams of carbohydrate, which is what I consume.Remember, what I’m showing you here is what I have been eating for about the last 7 months.For the first 20 months of my nutritional transformation, I was gradually reducing carbohydrate intake from about 600 daily grams to 300 daily grams to 150 daily grams.

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This coupling is particularly problematic given that matrix-imposed steric barriers can regulate invasion speed independent of mechanics.