Acidic matrix macromolecules play a crucial role in biological crystal growth. In vitro experiments showed that acidic proteins interact with specific crystal faces, which are stereochemically analogous. When proteins are adsorbed onto a rigid substrate, calcite crystals are nucleated on these faces. This stereochemical property is essential for the interaction with acidic proteins, which act as nucleators of calcite from the best interacting plane. Biologically formed crystals are common in many organisms, often with uniform size, oriented axes, and distinct shapes. These properties suggest controlled crystal growth, often starting with an organic matrix. Matrix macromolecules, many of which are acidic, regulate crystal growth through unknown mechanisms. In vitro studies have examined the effects of these macromolecules on crystal growth, revealing that specific interactions occur with certain crystal faces. The study used acidic proteins from mollusk shells to investigate interactions with various calcium dicarboxylate crystals and calcite. The proteins, which are aspartic acid-rich or serine-rich, interact with specific crystal faces. The aspartic acid-rich proteins, when adsorbed on a rigid substrate, nucleate calcite from the (001) plane. The stereochemical effect is attributed to the optimal coordination of calcium ions with carboxylate groups on the crystal surface. The results show that the stereochemical effect is essential for specific interactions, and that the arrangement of calcium and carboxylate ions on the crystal surface allows for cooperative binding. These findings highlight the importance of stereochemical requirements in biomineralization, emphasizing the role of acidic proteins in regulating crystal growth. The study also demonstrates that the presence of these proteins can influence the orientation and morphology of crystals, with implications for understanding the formation of biogenic calcite and aragonite. The results suggest that examining crystal faces can provide insights into nucleation sites, and that the stereochemical effect is crucial in determining crystal growth in biological systems.Acidic matrix macromolecules play a crucial role in biological crystal growth. In vitro experiments showed that acidic proteins interact with specific crystal faces, which are stereochemically analogous. When proteins are adsorbed onto a rigid substrate, calcite crystals are nucleated on these faces. This stereochemical property is essential for the interaction with acidic proteins, which act as nucleators of calcite from the best interacting plane. Biologically formed crystals are common in many organisms, often with uniform size, oriented axes, and distinct shapes. These properties suggest controlled crystal growth, often starting with an organic matrix. Matrix macromolecules, many of which are acidic, regulate crystal growth through unknown mechanisms. In vitro studies have examined the effects of these macromolecules on crystal growth, revealing that specific interactions occur with certain crystal faces. The study used acidic proteins from mollusk shells to investigate interactions with various calcium dicarboxylate crystals and calcite. The proteins, which are aspartic acid-rich or serine-rich, interact with specific crystal faces. The aspartic acid-rich proteins, when adsorbed on a rigid substrate, nucleate calcite from the (001) plane. The stereochemical effect is attributed to the optimal coordination of calcium ions with carboxylate groups on the crystal surface. The results show that the stereochemical effect is essential for specific interactions, and that the arrangement of calcium and carboxylate ions on the crystal surface allows for cooperative binding. These findings highlight the importance of stereochemical requirements in biomineralization, emphasizing the role of acidic proteins in regulating crystal growth. The study also demonstrates that the presence of these proteins can influence the orientation and morphology of crystals, with implications for understanding the formation of biogenic calcite and aragonite. The results suggest that examining crystal faces can provide insights into nucleation sites, and that the stereochemical effect is crucial in determining crystal growth in biological systems.