The article describes a method for preparing collagen substrata, specifically hydrated collagen lattices (HCLs), which are used to study cell behavior. HCLs contain 0.1% collagen by weight and have a 640 Å lateral period, resembling soft-tissue matrices. The preparation involves dissolving rat tail tendon collagen in a low-ionic-strength, low-pH solution and then precipitating it into a fluid medium to form the lattice. HCLs are characterized by their ultrastructure, stability, and ability to support cell growth and behavior. The authors demonstrate how HCLs can be used as two- and three-dimensional substrata for cell studies. They observe that human diploid fibroblasts attach, extend, and behave similarly on HCLs as they do on plastic, but with a distinct bipolar spindle form. The cells adhere strongly to HCLs and exhibit rapid movement, often deforming into pear shapes. The growth rate of normal fibroblasts on HCLs is generally slower than on plastic, but there is no significant difference at confluent densities. The article also examines the behavior of transformed cells, such as SVTR and HeLa cells, on HCLs. SVTR cells show a clustering behavior and fail to clone under the same conditions as normal cells, suggesting differences in their substrate requirements. HeLa cells clone readily within HCLs, forming uniform, compact colonies. The authors discuss the implications of these findings, noting that HCLs can reveal novel cellular behaviors and provide insights into how cells function in the body. They suggest that the ability of SVTR cells to clone within HCLs may reflect changes in their attachment to the extracellular matrix, which could have implications for tumor metastasis and focal growth at tumor fronts.The article describes a method for preparing collagen substrata, specifically hydrated collagen lattices (HCLs), which are used to study cell behavior. HCLs contain 0.1% collagen by weight and have a 640 Å lateral period, resembling soft-tissue matrices. The preparation involves dissolving rat tail tendon collagen in a low-ionic-strength, low-pH solution and then precipitating it into a fluid medium to form the lattice. HCLs are characterized by their ultrastructure, stability, and ability to support cell growth and behavior. The authors demonstrate how HCLs can be used as two- and three-dimensional substrata for cell studies. They observe that human diploid fibroblasts attach, extend, and behave similarly on HCLs as they do on plastic, but with a distinct bipolar spindle form. The cells adhere strongly to HCLs and exhibit rapid movement, often deforming into pear shapes. The growth rate of normal fibroblasts on HCLs is generally slower than on plastic, but there is no significant difference at confluent densities. The article also examines the behavior of transformed cells, such as SVTR and HeLa cells, on HCLs. SVTR cells show a clustering behavior and fail to clone under the same conditions as normal cells, suggesting differences in their substrate requirements. HeLa cells clone readily within HCLs, forming uniform, compact colonies. The authors discuss the implications of these findings, noting that HCLs can reveal novel cellular behaviors and provide insights into how cells function in the body. They suggest that the ability of SVTR cells to clone within HCLs may reflect changes in their attachment to the extracellular matrix, which could have implications for tumor metastasis and focal growth at tumor fronts.