APPLICATION:
DRUG SCREENING

By developing better disease models and including mechanics as a screening option, more options are opened for better drug screening opportunities. There is promise for improved disease models by using 3D tissues that are enhanced with mechanically relevant scaffolds. Additionally, testing of the mechanics of tissues can provide more information about the response of tissues to different drugs. These models show promise for cancer drug screening and for a variety of diseases that are now being modeled with spheroids.

Cancer

Cancer is a complex disease, and novel drugs can have adverse effects on healthy cells, including by affecting the mechanics. New models that use 3D tissues are being used to identify new therapeutics, as well as to identify potential problems with drugs that may cause unwanted side effects [1]. In one study, AFM was used to measure the mechanical properties of neuronal cells, and found significant changes when use of a chemotherapy drug was used. The authors identify their model as having the potential to be used as a marker for new drugs to ensure that they do not have adverse side effects [2]. In another study, the mechanics of tumors and the ECM were modeled and measured using a variety of tools to determine how different drugs affect tumor growth and ECM deterioration. The study also identified the potential for different inhibitors that maybe result in more effective therapies due to their findings [3].

Spheroids

Spheroids are an emerging tool to create 3D tissue models that create physiologically relevant matrix and combinations of cells. Mechanical measurements of spheroids have had promise as a way to measure the effects of drugs on the spheroids as determine if there are changes to the microenvironment [4]. In one study, nanoindentation was used to characterize the elasticity of novel hydrogels to improve liver spheroid models, and the improved model showed better performance of drug metabolism [5]. Another study used microwells to create spheroids and use nanoindentation to characterize the properties of the microwells to ensure that there was not degradation over time and that the wells had relevant mechanical properties [6].

Myocardium

The heart is a mechanical organ, and a key component in drug screening, as a novel drug must not adversely affect the heart. New techniques have been used to measure the mechanical properties of cardiac tissues as well as cells to improve drug screening methods [7]. One study investigated a drug affecting microtubules and used nanoindentation to compare the mechanical properties of cardiomyocytes with and without drug treatments. The study found that use mechanical measurements was able to improve understanding of the disease model and show how drugs can affect the heart [8]. Another study used nanoindentation to determine the maturation of an induced pluripotent stem cell model for cardiac drug development. They tuned the stiffness of hydrogels to mimic the stiffness of aged tissue samples and found that the stiffer tissue also affected the tissue function [9].