Mechanical stress response analysis of cells and tissues

Abstract

A method and device are disclosed for inducing mechanical stress in a cellular sample to evaluate mechanotransduction in the cellular sample. In one embodiment, the mechanical stress is induced by generating a microcavitation bubble in the cellular sample using a pulsed energy. The microcavitation bubble creates a microtsunami, which provides a transient, impulsive mechanical stress on the cellular sample, forming a gradient of effects at distances away from the microcavitation bubble.

What is claimed is: 
     
         1 . A method for discovery and/or screening of test compounds that may modulate cellular mechanotransduction, the method comprising:
 providing at least one cellular sample;   administering a test compound to the at least one cellular sample;   initiating a microcavitation bubble at a site within the at least one cellular sample;   monitoring a signal related to the cellular mechanotransduction of the at least one cellular sample; and   comparing the signal to a control signal, wherein a difference between the signal and the control signal indicates that the test compound modulates cellular mechanotransduction.   
     
     
         2 . The method of  claim 1 , wherein initiating the microcavitation bubble comprises applying an energy source to the site. 
     
     
         3 . The method of  claim 2 , wherein the energy source is selected from the group consisting of a laser, an ultrasonic transducer, a piezoelectric transducer, or combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the at least one cellular sample comprises cells adherent to a two-dimensional substrate. 
     
     
         5 . The method of  claim 1 , wherein the at least one cellular sample comprises a three-dimensional matrix. 
     
     
         6 . The method of  claim 5 , wherein the three-dimensional matrix is selected from the group consisting of a hydrogel, a tissue, a reconstituted tissue, an extracellular matrix, a tissue scaffold or combinations thereof. 
     
     
         7 . The method of  claim 1 , wherein the at least one cellular sample comprises a micro-patterned cellular sample configured to have some areas without cells. 
     
     
         8 . The method of  claim 1 , wherein the microcavitation bubble is configured to form a microtsunami. 
     
     
         9 . A method of testing a cellular response to a transient mechanical stimulus, the method comprising:
 providing a plurality of cellular samples;   administering a test compound to at least a first cellular sample, and a control vehicle to at least a second cellular sample;   initiating a microtsunami within at least the first and second cellular samples, wherein the test compound and control vehicle may be administered before, during, or after initiating the microtsunami;   monitoring a signal related to the cellular response in at least the first and second cellular samples; and   comparing the signals from at least the first and second cellular samples, wherein a difference between the signals indicates that the test compound modulates the cellular response to the transient mechanical stimulus.   
     
     
         10 . A device for high-throughput discovery and/or screening of test compounds that may modulate cellular mechanotransduction, the device comprising:
 a holder configured to hold at least one cellular sample;   an energy source configured to deliver energy along a path to a site within the at least one cellular sample, wherein the energy is sufficient to generate a microcavitation bubble at the site; and   a sensor configured to receive a signal from the at least one cellular sample, wherein the signal is related to cellular mechanotransduction.   
     
     
         11 . The device of  claim 10 , wherein the holder comprises:
 a movable stage configured to secure a dish comprising one or more wells, each well comprising a cellular sample;   an actuator configured to move the movable stage and position each of the one or more wells within the path of the energy; and   a controller configured to control the actuator.   
     
     
         12 . The device of  claim 10 , wherein the holder comprises:
 a stationary stage configured to secure a dish comprising one or more wells, each well comprising a cellular sample;   wherein the energy source is configured to move to direct energy to a site in each of the one or more wells.   
     
     
         13 . The device of  claim 10 , wherein the energy source is selected from a laser, an ultrasonic transducer, a piezoelectric transducer or combinations thereof. 
     
     
         14 . The device of  claim 10 , wherein the sensor comprises a multichannel sensor array configured to receive a more than one signals from the cellular sample.