Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment
Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment
 
  This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Young’s modulus of ?5 kPa. This is notably greater than that reported for isolated chondrocytes in suspension. The increase in cell modulus occurs over a 24-h period and is associated with an increase in the organization of the cortical actin cytoskeleton, which is known to regulate cell mechanics. However, there was a reduction in chromatin condensation, suggesting that changes in the nucleus mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed that cells in the stiffer gels rapidly develop a higher Young’s modulus of ?20 kPa, sixfold greater than that observed in the softer gels. This was associated with higher levels of actin organization and chromatin condensation, but only after 24 h in culture. Further studies revealed that cells in stiffer gels synthesize less extracellular matrix over a 28-day culture period. Hence, this study demonstrates that the properties of the three-dimensional microenvironment regulate the mechanical, structural, and metabolic properties of living cells
  
  
  1188-1197
  
    
      Chen, J.
      
        116323ca-c4fd-4be2-96cb-a54d6cec5cc4
      
     
  
    
      Irianto, J.
      
        771f6f0d-ad0b-446c-be14-46c238744812
      
     
  
    
      Inamdar, S.
      
        454d9194-48cd-4f61-a5a2-04e010d6dabc
      
     
  
    
      Pravincumar, P.
      
        6b64d04a-9921-478e-ac22-0d1baf89e4c7
      
     
  
    
      Lee, D.A.
      
        fbbf7169-d08b-4deb-ae87-a2cbd97c58e7
      
     
  
    
      Bader, Dan L.
      
        9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
      
     
  
    
      Knight, M.M.
      
        eaff1c5c-595c-4b27-bb12-654dcfa0c1cb
      
     
  
  
   
  
  
    
      19 September 2012
    
    
  
  
    
      Chen, J.
      
        116323ca-c4fd-4be2-96cb-a54d6cec5cc4
      
     
  
    
      Irianto, J.
      
        771f6f0d-ad0b-446c-be14-46c238744812
      
     
  
    
      Inamdar, S.
      
        454d9194-48cd-4f61-a5a2-04e010d6dabc
      
     
  
    
      Pravincumar, P.
      
        6b64d04a-9921-478e-ac22-0d1baf89e4c7
      
     
  
    
      Lee, D.A.
      
        fbbf7169-d08b-4deb-ae87-a2cbd97c58e7
      
     
  
    
      Bader, Dan L.
      
        9884d4f6-2607-4d48-bf0c-62bdcc0d1dbf
      
     
  
    
      Knight, M.M.
      
        eaff1c5c-595c-4b27-bb12-654dcfa0c1cb
      
     
  
       
    
 
  
    
      
  
  
  
  
  
  
    Chen, J., Irianto, J., Inamdar, S., Pravincumar, P., Lee, D.A., Bader, Dan L. and Knight, M.M.
  
  
  
  
   
    (2012)
  
  
    
    Cell mechanics, structure, and function are regulated by the stiffness of the three-dimensional microenvironment.
  
  
  
  
    Biophysical Journal, 103 (6), .
  
   (doi:10.1016/j.bpj.2012.07.054). 
  
  
  
    (PMID:22995491)
   
  
  
  
  
  
   
  
    
      
        
          Abstract
          This study adopts a combined computational and experimental approach to determine the mechanical, structural, and metabolic properties of isolated chondrocytes cultured within three-dimensional hydrogels. A series of linear elastic and hyperelastic finite-element models demonstrated that chondrocytes cultured for 24 h in gels for which the relaxation modulus is <5 kPa exhibit a cellular Young’s modulus of ?5 kPa. This is notably greater than that reported for isolated chondrocytes in suspension. The increase in cell modulus occurs over a 24-h period and is associated with an increase in the organization of the cortical actin cytoskeleton, which is known to regulate cell mechanics. However, there was a reduction in chromatin condensation, suggesting that changes in the nucleus mechanics may not be involved. Comparison of cells in 1% and 3% agarose showed that cells in the stiffer gels rapidly develop a higher Young’s modulus of ?20 kPa, sixfold greater than that observed in the softer gels. This was associated with higher levels of actin organization and chromatin condensation, but only after 24 h in culture. Further studies revealed that cells in stiffer gels synthesize less extracellular matrix over a 28-day culture period. Hence, this study demonstrates that the properties of the three-dimensional microenvironment regulate the mechanical, structural, and metabolic properties of living cells
        
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      Published date: 19 September 2012
 
    
  
  
    
  
    
  
    
  
    
  
    
  
    
  
    
     
        Organisations:
        Faculty of Health Sciences
      
    
  
    
  
  
        Identifiers
        Local EPrints ID: 347080
        URI: http://eprints.soton.ac.uk/id/eprint/347080
        
          
        
        
        
          ISSN: 0006-3495
        
        
          PURE UUID: 76fb7bcd-5e95-4989-9392-fa73be8a6ce1
        
  
    
        
          
        
    
        
          
        
    
        
          
        
    
        
          
        
    
        
          
        
    
        
          
            
              
            
          
        
    
        
          
        
    
  
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  Date deposited: 17 Jan 2013 12:03
  Last modified: 14 Mar 2024 12:45
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      Contributors
      
          
          Author:
          
            
            
              J. Chen
            
          
        
      
          
          Author:
          
            
            
              J. Irianto
            
          
        
      
          
          Author:
          
            
            
              S. Inamdar
            
          
        
      
          
          Author:
          
            
            
              P. Pravincumar
            
          
        
      
          
          Author:
          
            
            
              D.A. Lee
            
          
        
      
        
      
          
          Author:
          
            
            
              M.M. Knight
            
          
        
      
      
      
    
  
   
  
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