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Understanding the particulate nature of matter (PNM) is one of the foundational but challenging concepts in secondary science education. While previous research has investigated students’ misconceptions in understanding PNM, the effect of learning sequences (i.e., micro-to-macro and macro-to-micro) remains understudied. This mixed method research empirically compared the effects of two learning sequences on seventh-grade students’ (N=69, ages 12-13) comprehension of the PNM. We found female students achieved significantly higher predicted posttest scores under the macro-to-micro sequence. In contrast, no significant difference was observed between the two learning sequences for male students. The findings reveal that females benefits more from a macro-to-micro approach, suggesting that tailored strategies may optimize conceptual understanding of the particulate nature of matter across diverse learners.